E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Special Issue "Signal Transduction of Tissue Repair"

Quicklinks

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology".

Deadline for manuscript submissions: closed (30 July 2014)

Special Issue Editor

Guest Editor
Dr. Regina M. Day (Website)

Department of Pharmacology, The Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA
Phone: 301-295-3236
Interests: cell biology and signal transduction of normal tissue repair and fibrotic remodeling in the lung; adult stem cells that participate in lung repair; apoptosis; cytoskeletal rearrangement; cellular senescence and inflammation; reactive oxygen species in signal transduction and antioxidant cellular defenses

Special Issue Information

Dear Colleagues,

Tissue homeostasis requires the capacity for normal repair.  In a number of tissues, repair processes have been demonstrated to involve complex and sometimes interrelated events, including signaling from the initial injury, inflammation, cell recruitment and proliferation, and eventually remodeling or restoration of normal tissue. Although initial stages of tissue repair also involve inflammatory responses and the activation of mesenchymal cells, specific inhibitory signals are required to ensure that overwhelming levels of inflammation and fibrotic repair to not predominate, which would result in scarring and dysfunctional tissue. Different tissues in the adult vary greatly in their ability to regenerate normal architecture with normal function.  For instance, the liver displays robust repair functions, while tissues such as the heart and lungs have more limited repair capabilities. Research investigating tissue regeneration has revealed a number of factors affect repair activities, including the abundance or paucity of specific adult stem cells, vascularization, microenvironment alterations, and the production of growth factors to effectively induce proliferation of the appropriate cell types for repair. This Special Issue will examine signal transduction pathways involved in tissue repair. In this issue, an emphasis will be placed on research and review articles examining mechanisms of signal transduction involved in normal tissue repair pathways, including those shown to induce proliferation and migration of adult stem cells. Signaling networks that govern wound and repair microenvironments, mesencymal-epithelial transition (MET) for the generation of pluripotent stem cells, and the regulation of factors and cytokines required for tissue repair will also be highlighted. Other topics for consideration include studies of tissue-specific adult stem cells; signaling mechanisms for the inhibition of fibrosis and inflammation related to the promotion of normal tissue repair; epithelial-mesenchymal-transformation (EMT) for tissue repair; and signaling in vertebrate limb regeneration.  I encourage you to submit a manuscript to this issue dedicated to the exploration of current research in the tissue repair field.

Dr. Regina M. Day
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs).

Keywords

  • tissue repair
  • signaling pathways
  • adult stem cells
  • pluripotent cell reprogramming
  • growth factor regulation for tissue repair
  • cellular proliferation for tissue repair
  • cell migration for tissue repair
  • wound microenvironment
  • injury-induced inflammation
  • epithelial-mesenchymal transformation
  • mesenchymal-epithelial transformation

Published Papers (13 papers)

View options order results:
result details:
Displaying articles 1-13
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle Endothelial Semaphorin 7A Promotes Inflammation in Seawater Aspiration-Induced Acute Lung Injury
Int. J. Mol. Sci. 2014, 15(11), 19650-19661; doi:10.3390/ijms151119650
Received: 20 August 2014 / Revised: 30 September 2014 / Accepted: 15 October 2014 / Published: 28 October 2014
PDF Full-text (3192 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Inflammation is involved in the pathogenesis of seawater aspiration-induced acute lung injury (ALI). Although several studies have shown that Semaphorin 7A (SEMA7A) promotes inflammation, there are limited reports regarding immunological function of SEMA7A in seawater aspiration-induced ALI. Therefore, we investigated the role [...] Read more.
Inflammation is involved in the pathogenesis of seawater aspiration-induced acute lung injury (ALI). Although several studies have shown that Semaphorin 7A (SEMA7A) promotes inflammation, there are limited reports regarding immunological function of SEMA7A in seawater aspiration-induced ALI. Therefore, we investigated the role of SEMA7A during seawater aspiration-induced ALI. Male Sprague–Dawley rats were underwent seawater instillation. Then, lung samples were collected at an indicated time for analysis. In addition, rat pulmonary microvascular endothelial cells (RPMVECs) were cultured and then stimulated with 25% seawater for indicated time point. After these treatments, cells samples were collected for analysis. In vivo, seawater instillation induced lung histopathologic changes, pro-inflammation cytokines release and increased expression of SEMA7A. In vitro, seawater stimulation led to pro-inflammation cytokine release, cytoskeleton remodeling and increased monolayer permeability in pulmonary microvascular endothelial cells. In addition, knockdown of hypoxia-inducible factor (HIF)-1α inhibited the seawater induced increase expression of SEMA7A. Meanwhile, knockdown of SEMA7A by specific siRNA inhibited the seawater induced aberrant inflammation, endothelial cytoskeleton remodeling and endothelial permeability. These results suggest that SEMA7A is critical in the development of lung inflammation and pulmonary edema in seawater aspiration-induced ALI, and may be a therapeutic target for this disease. Full article
(This article belongs to the Special Issue Signal Transduction of Tissue Repair)
Open AccessArticle Emodin Ameliorates LPS-Induced Acute Lung Injury, Involving the Inactivation of NF-κB in Mice
Int. J. Mol. Sci. 2014, 15(11), 19355-19368; doi:10.3390/ijms151119355
Received: 15 August 2014 / Revised: 15 October 2014 / Accepted: 17 October 2014 / Published: 24 October 2014
Cited by 7 | PDF Full-text (1909 KB) | HTML Full-text | XML Full-text
Abstract
Acute lung injury (ALI) and its severe manifestation of acute respiratory distress syndrome (ARDS) are well-known illnesses. Uncontrolled and self-amplified pulmonary inflammation lies at the center of the pathology of this disease. Emodin, the bio-active coxund of herb Radix rhizoma Rhei, shows [...] Read more.
Acute lung injury (ALI) and its severe manifestation of acute respiratory distress syndrome (ARDS) are well-known illnesses. Uncontrolled and self-amplified pulmonary inflammation lies at the center of the pathology of this disease. Emodin, the bio-active coxund of herb Radix rhizoma Rhei, shows potent anti-inflammatory properties through inactivation of nuclear factor-κB (NF-κB). The aim of this study was to evaluate the effect of emodin on lipopolysaccharide (LPS)-induced ALI in mice, and its potential bio-mechanism. In our study, BALB/c mice were stimulated with LPS to induce ALI. After 72 h of LPS stimulation, pulmonary pathological changes, lung injury scores, pulmonary edema, myeloperoxidase (MPO) activity, total cells, neutrophils, macrophages, TNF-α, IL-6 and IL-1β in bronchoalveolar lavage fluid (BALF), and MCP-1 and E-selectin expression were notably attenuated by emodin in mice. Meanwhile, our data also revealed that emodin significantly inhibited the LPS-enhanced the phosphorylation of NF-κB p65 and NF-κB p65 DNA binding activity in lung. Our data indicates that emodin potently inhibits LPS-induced pulmonary inflammation, pulmonary edema and MCP-1 and E-selectin expression, and that these effects were very likely mediated by inactivation of NF-κB in mice. These results suggest a therapeutic potential of emodin as an anti-inflammatory agent for ALI/ARDS treatment. Full article
(This article belongs to the Special Issue Signal Transduction of Tissue Repair)
Open AccessArticle Overexpression of Shox2 Leads to Congenital Dysplasia of the Temporomandibular Joint in Mice
Int. J. Mol. Sci. 2014, 15(8), 13135-13150; doi:10.3390/ijms150813135
Received: 3 April 2014 / Revised: 18 May 2014 / Accepted: 26 June 2014 / Published: 24 July 2014
Cited by 3 | PDF Full-text (6958 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Our previous study reported that inactivation of Shox2 led to dysplasia and ankylosis of the temporomandibular joint (TMJ), and that replacing Shox2 with human Shox partially rescued the phenotype with a prematurely worn out articular disc. However, the mechanisms of Shox2 activity [...] Read more.
Our previous study reported that inactivation of Shox2 led to dysplasia and ankylosis of the temporomandibular joint (TMJ), and that replacing Shox2 with human Shox partially rescued the phenotype with a prematurely worn out articular disc. However, the mechanisms of Shox2 activity in TMJ development remain to be elucidated. In this study, we investigated the molecular and cellular basis for the congenital dysplasia of TMJ in Wnt1-Cre; pMes-stop Shox2 mice. We found that condyle and glenoid fossa dysplasia occurs primarily in the second week after the birth. The dysplastic TMJ of Wnt1-Cre; pMes-stop Shox2 mice exhibits a loss of Collagen type I, Collagen type II, Ihh and Gli2. In situ zymography and immunohistochemistry further demonstrate an up-regulation of matrix metalloproteinases (MMPs), MMP9 and MMP13, accompanied by a significantly increased cell apoptosis. In addition, the cell proliferation and expressions of Sox9, Runx2 and Ihh are no different in the embryonic TMJ between the wild type and mutant mice. Our results show that overexpression of Shox2 leads to the loss of extracellular matrix and the increase of cell apoptosis in TMJ dysplasia by up-regulating MMPs and down-regulating the Ihh signaling pathway. Full article
(This article belongs to the Special Issue Signal Transduction of Tissue Repair)
Figures

Open AccessArticle Lyophilized Platelet-Rich Fibrin (PRF) Promotes Craniofacial Bone Regeneration through Runx2
Int. J. Mol. Sci. 2014, 15(5), 8509-8525; doi:10.3390/ijms15058509
Received: 5 March 2014 / Revised: 1 April 2014 / Accepted: 15 April 2014 / Published: 14 May 2014
Cited by 6 | PDF Full-text (4758 KB) | HTML Full-text | XML Full-text
Abstract
Freeze-drying is an effective means to control scaffold pore size and preserve its composition. The purpose of the present study was to determine the applicability of lyophilized Platelet-rich fibrin (LPRF) as a scaffold for craniofacial tissue regeneration and to compare its biological [...] Read more.
Freeze-drying is an effective means to control scaffold pore size and preserve its composition. The purpose of the present study was to determine the applicability of lyophilized Platelet-rich fibrin (LPRF) as a scaffold for craniofacial tissue regeneration and to compare its biological effects with commonly used fresh Platelet-rich fibrin (PRF). LPRF caused a 4.8-fold ± 0.4-fold elevation in Runt-related transcription factor 2 (Runx2) expression in alveolar bone cells, compared to a 3.6-fold ± 0.2-fold increase when using fresh PRF, and a more than 10-fold rise of alkaline phosphatase levels and mineralization markers. LPRF-induced Runx2 expression only occurred in alveolar bone and not in periodontal or dental follicle cells. LPRF also caused a 1.6-fold increase in osteoblast proliferation (p < 0.001) when compared to fresh PRF. When applied in a rat craniofacial defect model for six weeks, LPRF resulted in 97% bony coverage of the defect, compared to 84% for fresh PRF, 64% for fibrin, and 16% without scaffold. Moreover, LPRF thickened the trabecular diameter by 25% when compared to fresh PRF and fibrin, and only LPRF and fresh PRF resulted in the formation of interconnected trabeculae across the defect. Together, these studies support the application of lyophilized PRF as a biomimetic scaffold for craniofacial bone regeneration and mineralized tissue engineering. Full article
(This article belongs to the Special Issue Signal Transduction of Tissue Repair)

Review

Jump to: Research

Open AccessReview Hypoxic Signaling During Tissue Repair and Regenerative Medicine
Int. J. Mol. Sci. 2014, 15(11), 19791-19815; doi:10.3390/ijms151119791
Received: 6 August 2014 / Revised: 12 September 2014 / Accepted: 15 October 2014 / Published: 31 October 2014
Cited by 8 | PDF Full-text (1468 KB) | HTML Full-text | XML Full-text
Abstract
In patients with chronic wounds, autologous tissue repair is often not sufficient to heal the wound. These patients might benefit from regenerative medicine or the implantation of a tissue-engineered scaffold. Both wound healing and tissue engineering is dependent on the formation of [...] Read more.
In patients with chronic wounds, autologous tissue repair is often not sufficient to heal the wound. These patients might benefit from regenerative medicine or the implantation of a tissue-engineered scaffold. Both wound healing and tissue engineering is dependent on the formation of a microvascular network. This process is highly regulated by hypoxia and the transcription factors hypoxia-inducible factors-1α (HIF-1α) and -2α (HIF-2α). Even though much is known about the function of HIF-1α in wound healing, knowledge about the function of HIF-2α in wound healing is lacking. This review focuses on the function of HIF-1α and HIF-2α in microvascular network formation, wound healing, and therapy strategies. Full article
(This article belongs to the Special Issue Signal Transduction of Tissue Repair)
Open AccessReview FOXO1, TGF-β Regulation and Wound Healing
Int. J. Mol. Sci. 2014, 15(9), 16257-16269; doi:10.3390/ijms150916257
Received: 7 April 2014 / Revised: 13 August 2014 / Accepted: 14 August 2014 / Published: 15 September 2014
Cited by 18 | PDF Full-text (1037 KB) | HTML Full-text | XML Full-text
Abstract
Re-epithelialization is a complex process that involves migration and proliferation of keratinocytes, in addition to the production of cytokines and growth factors that affect other cells. The induction of transcription factors during these processes is crucial for successful wound healing. The transcription [...] Read more.
Re-epithelialization is a complex process that involves migration and proliferation of keratinocytes, in addition to the production of cytokines and growth factors that affect other cells. The induction of transcription factors during these processes is crucial for successful wound healing. The transcription factor forkhead boxO-1 (FOXO1) has recently been found to be an important regulator of wound healing. In particular, FOXO1 has significant effects through regulation of transforming growth factor-beta (TGF-β) expression and protecting keratinocytes from oxidative stress. In the absence of FOXO1, there is increased oxidative damage, reduced TGF-β1 expression, reduced migration and proliferation of keratinocytes and increased keratinocytes apoptosis leading to impaired re-epithelialization of wounds. Full article
(This article belongs to the Special Issue Signal Transduction of Tissue Repair)
Open AccessReview Erythropoietin Action in Stress Response, Tissue Maintenance and Metabolism
Int. J. Mol. Sci. 2014, 15(6), 10296-10333; doi:10.3390/ijms150610296
Received: 20 February 2014 / Revised: 23 May 2014 / Accepted: 28 May 2014 / Published: 10 June 2014
Cited by 20 | PDF Full-text (2646 KB) | HTML Full-text | XML Full-text
Abstract
Erythropoietin (EPO) regulation of red blood cell production and its induction at reduced oxygen tension provides for the important erythropoietic response to ischemic stress. The cloning and production of recombinant human EPO has led to its clinical use in patients with anemia [...] Read more.
Erythropoietin (EPO) regulation of red blood cell production and its induction at reduced oxygen tension provides for the important erythropoietic response to ischemic stress. The cloning and production of recombinant human EPO has led to its clinical use in patients with anemia for two and half decades and has facilitated studies of EPO action. Reports of animal and cell models of ischemic stress in vitro and injury suggest potential EPO benefit beyond red blood cell production including vascular endothelial response to increase nitric oxide production, which facilitates oxygen delivery to brain, heart and other non-hematopoietic tissues. This review discusses these and other reports of EPO action beyond red blood cell production, including EPO response affecting metabolism and obesity in animal models. Observations of EPO activity in cell and animal model systems, including mice with tissue specific deletion of EPO receptor (EpoR), suggest the potential for EPO response in metabolism and disease. Full article
(This article belongs to the Special Issue Signal Transduction of Tissue Repair)
Open AccessReview NOD-Like Receptors in Intestinal Homeostasis and Epithelial Tissue Repair
Int. J. Mol. Sci. 2014, 15(6), 9594-9627; doi:10.3390/ijms15069594
Received: 20 March 2014 / Revised: 16 May 2014 / Accepted: 20 May 2014 / Published: 30 May 2014
Cited by 9 | PDF Full-text (499 KB) | HTML Full-text | XML Full-text
Abstract
The intestinal epithelium constitutes a dynamic physical barrier segregating the luminal content from the underlying mucosal tissue. Following injury, the epithelial integrity is restored by rapid migration of intestinal epithelial cells (IECs) across the denuded area in a process known as wound [...] Read more.
The intestinal epithelium constitutes a dynamic physical barrier segregating the luminal content from the underlying mucosal tissue. Following injury, the epithelial integrity is restored by rapid migration of intestinal epithelial cells (IECs) across the denuded area in a process known as wound healing. Hence, through a sequence of events involving restitution, proliferation and differentiation of IECs the gap is resealed and homeostasis reestablished. Relapsing damage followed by healing of the inflamed mucosa is a hallmark of several intestinal disorders including inflammatory bowel diseases (IBD). While several regulatory peptides, growth factors and cytokines stimulate restitution of the epithelial layer after injury, recent evidence in the field underscores the contribution of innate immunity in controlling this process. In particular, nucleotide-binding and oligomerization domain-like receptors (NLRs) play critical roles in sensing the commensal microbiota, maintaining homeostasis, and regulating intestinal inflammation. Here, we review the process of intestinal epithelial tissue repair and we specifically focus on the impact of NLR-mediated signaling mechanisms involved in governing epithelial wound healing during disease. Full article
(This article belongs to the Special Issue Signal Transduction of Tissue Repair)
Figures

Open AccessReview Adipose-Derived Stem Cells: A Review of Signaling Networks Governing Cell Fate and Regenerative Potential in the Context of Craniofacial and Long Bone Skeletal Repair
Int. J. Mol. Sci. 2014, 15(6), 9314-9330; doi:10.3390/ijms15069314
Received: 13 February 2014 / Revised: 16 May 2014 / Accepted: 20 May 2014 / Published: 26 May 2014
Cited by 10 | PDF Full-text (236 KB) | HTML Full-text | XML Full-text
Abstract
Improvements in medical care, nutrition and social care are resulting in a commendable change in world population demographics with an ever increasing skew towards an aging population. As the proportion of the world’s population that is considered elderly increases, so does the [...] Read more.
Improvements in medical care, nutrition and social care are resulting in a commendable change in world population demographics with an ever increasing skew towards an aging population. As the proportion of the world’s population that is considered elderly increases, so does the incidence of osteodegenerative disease and the resultant burden on healthcare. The increasing demand coupled with the limitations of contemporary approaches, have provided the impetus to develop novel tissue regeneration therapies. The use of stem cells, with their potential for self-renewal and differentiation, is one potential solution. Adipose-derived stem cells (ASCs), which are relatively easy to harvest and readily available have emerged as an ideal candidate. In this review, we explore the potential for ASCs to provide tangible therapies for craniofacial and long bone skeletal defects, outline key signaling pathways that direct these cells and describe how the developmental signaling program may provide clues on how to guide these cells in vivo. This review also provides an overview of the importance of establishing an osteogenic microniche using appropriately customized scaffolds and delineates some of the key challenges that still need to be overcome for adult stem cell skeletal regenerative therapy to become a clinical reality. Full article
(This article belongs to the Special Issue Signal Transduction of Tissue Repair)
Open AccessReview Signaling Pathways in Cartilage Repair
Int. J. Mol. Sci. 2014, 15(5), 8667-8698; doi:10.3390/ijms15058667
Received: 25 February 2014 / Revised: 28 April 2014 / Accepted: 4 May 2014 / Published: 15 May 2014
Cited by 15 | PDF Full-text (367 KB) | HTML Full-text | XML Full-text
Abstract
In adult healthy cartilage, chondrocytes are in a quiescent phase characterized by a fine balance between anabolic and catabolic activities. In ageing, degenerative joint diseases and traumatic injuries of cartilage, a loss of homeostatic conditions and an up-regulation of catabolic pathways occur. [...] Read more.
In adult healthy cartilage, chondrocytes are in a quiescent phase characterized by a fine balance between anabolic and catabolic activities. In ageing, degenerative joint diseases and traumatic injuries of cartilage, a loss of homeostatic conditions and an up-regulation of catabolic pathways occur. Since cartilage differentiation and maintenance of homeostasis are finely tuned by a complex network of signaling molecules and biophysical factors, shedding light on these mechanisms appears to be extremely relevant for both the identification of pathogenic key factors, as specific therapeutic targets, and the development of biological approaches for cartilage regeneration. This review will focus on the main signaling pathways that can activate cellular and molecular processes, regulating the functional behavior of cartilage in both physiological and pathological conditions. These networks may be relevant in the crosstalk among joint compartments and increased knowledge in this field may lead to the development of more effective strategies for inducing cartilage repair. Full article
(This article belongs to the Special Issue Signal Transduction of Tissue Repair)
Open AccessReview Alteration of Skin Properties with Autologous Dermal Fibroblasts
Int. J. Mol. Sci. 2014, 15(5), 8407-8427; doi:10.3390/ijms15058407
Received: 21 March 2014 / Revised: 19 April 2014 / Accepted: 6 May 2014 / Published: 13 May 2014
Cited by 11 | PDF Full-text (834 KB) | HTML Full-text | XML Full-text
Abstract
Dermal fibroblasts are mesenchymal cells found between the skin epidermis and subcutaneous tissue. They are primarily responsible for synthesizing collagen and glycosaminoglycans; components of extracellular matrix supporting the structural integrity of the skin. Dermal fibroblasts play a pivotal role in cutaneous wound [...] Read more.
Dermal fibroblasts are mesenchymal cells found between the skin epidermis and subcutaneous tissue. They are primarily responsible for synthesizing collagen and glycosaminoglycans; components of extracellular matrix supporting the structural integrity of the skin. Dermal fibroblasts play a pivotal role in cutaneous wound healing and skin repair. Preclinical studies suggest wider applications of dermal fibroblasts ranging from skin based indications to non-skin tissue regeneration in tendon repair. One clinical application for autologous dermal fibroblasts has been approved by the Food and Drug Administration (FDA) while others are in preclinical development or various stages of regulatory approval. In this context, we outline the role of fibroblasts in wound healing and discuss recent advances and the current development pipeline for cellular therapies using autologous dermal fibroblasts. The microanatomic and phenotypic differences of fibroblasts occupying particular locations within the skin are reviewed, emphasizing the therapeutic relevance of attributes exhibited by subpopulations of fibroblasts. Special focus is provided to fibroblast characteristics that define regional differences in skin, including the thick and hairless skin of the palms and soles as compared to hair-bearing skin. This regional specificity and functional identity of fibroblasts provides another platform for developing regional skin applications such as the induction of hair follicles in bald scalp or alteration of the phenotype of stump skin in amputees to better support their prosthetic devices. Full article
(This article belongs to the Special Issue Signal Transduction of Tissue Repair)
Open AccessReview The Role of Pericytes in Neurovascular Unit Remodeling in Brain Disorders
Int. J. Mol. Sci. 2014, 15(4), 6453-6474; doi:10.3390/ijms15046453
Received: 17 February 2014 / Revised: 1 April 2014 / Accepted: 8 April 2014 / Published: 16 April 2014
Cited by 11 | PDF Full-text (719 KB) | HTML Full-text | XML Full-text
Abstract
Neurons are extremely vulnerable cells that tightly rely on the brain’s highly dynamic and complex vascular network that assures an accurate and adequate distribution of nutrients and oxygen. The neurovascular unit (NVU) couples neuronal activity to vascular function, controls brain homeostasis, and [...] Read more.
Neurons are extremely vulnerable cells that tightly rely on the brain’s highly dynamic and complex vascular network that assures an accurate and adequate distribution of nutrients and oxygen. The neurovascular unit (NVU) couples neuronal activity to vascular function, controls brain homeostasis, and maintains an optimal brain microenvironment adequate for neuronal survival by adjusting blood-brain barrier (BBB) parameters based on brain needs. The NVU is a heterogeneous structure constituted by different cell types that includes pericytes. Pericytes are localized at the abluminal side of brain microvessels and contribute to NVU function. Pericytes play essential roles in the development and maturation of the neurovascular system during embryogenesis and stability during adulthood. Initially, pericytes were described as contractile cells involved in controlling neurovascular tone. However, recent reports have shown that pericytes dynamically respond to stress induced by injury upon brain diseases, by chemically and physically communicating with neighboring cells, by their immune properties and by their potential pluripotent nature within the neurovascular niche. As such, in this paper, we would like to review the role of pericytes in NVU remodeling, and their potential as targets for NVU repair strategies and consequently neuroprotection in two pathophysiologically distinct brain disorders: ischemic stroke and Alzheimer’s disease (AD). Full article
(This article belongs to the Special Issue Signal Transduction of Tissue Repair)
Figures

Open AccessReview Signal Transduction of Platelet-Induced Liver Regeneration and Decrease of Liver Fibrosis
Int. J. Mol. Sci. 2014, 15(4), 5412-5425; doi:10.3390/ijms15045412
Received: 23 February 2014 / Revised: 16 March 2014 / Accepted: 20 March 2014 / Published: 28 March 2014
Cited by 5 | PDF Full-text (299 KB) | HTML Full-text | XML Full-text
Abstract
Platelets contain three types of granules: alpha granules, dense granules, and lysosomal granules. Each granule contains various growth factors, cytokines, and other physiological substances. Platelets trigger many kinds of biological responses, such as hemostasis, wound healing, and tissue regeneration. This review presents [...] Read more.
Platelets contain three types of granules: alpha granules, dense granules, and lysosomal granules. Each granule contains various growth factors, cytokines, and other physiological substances. Platelets trigger many kinds of biological responses, such as hemostasis, wound healing, and tissue regeneration. This review presents experimental evidence of platelets in accelerating liver regeneration and improving liver fibrosis. The regenerative effect of liver by platelets consists of three mechanisms; i.e., the direct effect on hepatocytes, the cooperative effect with liver sinusoidal endothelial cells, and the collaborative effect with Kupffer cells. Many signal transduction pathways are involved in hepatocyte proliferation. One is activation of Akt and extracellular signal-regulated kinase (ERK)1/2, which are derived from direct stimulation from growth factors in platelets. The other is signal transducer and activator of transcription-3 (STAT3) activation by interleukin (IL)-6 derived from liver sinusoidal endothelial cells and Kupffer cells, which are stimulated by contact with platelets during liver regeneration. Platelets also improve liver fibrosis in rodent models by inactivating hepatic stellate cells to decrease collagen production. The level of intracellular cyclic adenosine monophosphate (cyclic AMP) is increased by adenosine through its receptors on hepatic stellate cells, resulting in inactivation of these cells. Adenosine is produced by the degradation of adenine nucleotides such as adenosine diphosphate (ADP) and adenosine tri-phosphate (ATP), which are stored in abundance within the dense granules of platelets. Full article
(This article belongs to the Special Issue Signal Transduction of Tissue Repair)

Journal Contact

MDPI AG
IJMS Editorial Office
St. Alban-Anlage 66, 4052 Basel, Switzerland
ijms@mdpi.com
Tel. +41 61 683 77 34
Fax: +41 61 302 89 18
Editorial Board
Contact Details Submit to IJMS
Back to Top