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Biomedicines
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Fibrosis vs Regeneration of Skin
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Fibrosis vs Regeneration of Skin

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 8587

Special Issue Editors

Dr. Ryoichi Mori

E-Mail Website
Guest Editor
Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, Japan
Interests: skin wound healing; microrna; inflammation; live imaging
Special Issues, Collections and Topics in MDPI journals
Dr. Kazuo Kishi

E-Mail Website
Guest Editor
Department of Plastic and Reconstructive Surgery, Keio University School of Medicine, Tokyo, Japan
Interests: regeneration; skin; fetus
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

When adult animals suffer a wound, scars form upon healing. In humans, depending on the constitution and the circumstances of the wound, a keloid may grow instead. By contrast, fetus skin regenerates completely up to a certain developmental stage. In addition, in some animal species, the phenomenon of hair follicles regenerating in the center of large wounds has been reported. With regard to skin, fibrosis and regeneration are two mostly separate phenomena. Complete regeneration means regeneration of the three-dimensional structure of dermal extra cellular matrix (ECM), hair follicles, skin appendages, and skin texture, but regeneration of ECM and skin texture are thought to be regulated by different mechanisms. In this volume, we will consider what promotes or hinders complete skin regeneration from these different perspectives.

Dr. Ryoichi Mori
Dr. Kazuo Kishi
Guest Editors

Manuscript Submission Information

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. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short 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 thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines 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 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • skin
  • scar
  • regeneration
  • hair
  • fibrosis

Published Papers (5 papers)

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Research

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10 pages, 5942 KiB  
Article
circRNAs May Be Involved in Dysfunction of Neutrophils of Type 2 Diabetic Mice through Regulation of Specific miRNAs
by Takahiro Umehara, Ryoichi Mori, Kimberly A. Mace, Katsumi Tanaka, Noriho Sakamoto, Kazuya Ikematsu and Hiroaki Sato
Biomedicines 2022, 10(12), 3129; https://doi.org/10.3390/biomedicines10123129 - 4 Dec 2022
Viewed by 1350
Abstract
Diabetes is known to delay wound healing, and this delay is attributed to prolonged inflammation. We found that microRNAs (miRNAs) might be involved in the dysfunction of diabetic-derived neutrophils, and dynamics of neutrophil and chronic inflammation might be initiated by miRNA-regulated genes. Moreover, [...] Read more.
Diabetes is known to delay wound healing, and this delay is attributed to prolonged inflammation. We found that microRNAs (miRNAs) might be involved in the dysfunction of diabetic-derived neutrophils, and dynamics of neutrophil and chronic inflammation might be initiated by miRNA-regulated genes. Moreover, studies of miRNA function in nephropathy have suggested that circular RNAs (circRNAs), which function as sponges of miRNA to regulate their expression, are potential biomarkers and new therapeutic targets for the diagnosis of diabetic nephropathy. Accordingly, to investigate the molecular mechanism of the regulation of inflammation in diabetic-derived neutrophils, we identified circRNAs in diabetic-derived neutrophils obtained from BKS.Cg-Dock7m +/+ Leprdb/J (Leprdb/db and Leprdb/+) mice using microarrays. Neutrophils from pooled bone marrow of three diabetic and three non-diabetic mice were isolated and total RNA was extracted. Microarray analysis was performed using the Arraystar Mouse Circular RNA Array. The results showed that three circRNAs were significantly increased and six circRNAs were significantly decreased in diabetic-derived neutrophils compared with non-diabetic-derived neutrophils. The expressions of some circRNAs in diabetic-derived neutrophils were more than double those in non-diabetic-derived neutrophils. The circRNAs contain binding sites of miRNAs, which were differentially expressed in diabetic-derived neutrophils. Our results suggest that circRNAs may be involved in the regulation of inflammation in diabetic-derived neutrophils. Full article
(This article belongs to the Special Issue Fibrosis vs Regeneration of Skin)
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16 pages, 22210 KiB  
Article
Local Glucocorticoid Administration Impairs Embryonic Wound Healing
by Martin Bablok, Morris Gellisch, Beate Brand-Saberi and Gabriela Morosan-Puopolo
Biomedicines 2022, 10(12), 3125; https://doi.org/10.3390/biomedicines10123125 - 3 Dec 2022
Cited by 2 | Viewed by 1673
Abstract
Understanding the complex processes of fetal wound healing and skin regeneration can help to improve fetal surgery. As part of the integumentary system, the skin protects the newborn organism against environmental factors and serves various functions. Glucocorticoids can enter the fetal circulatory system [...] Read more.
Understanding the complex processes of fetal wound healing and skin regeneration can help to improve fetal surgery. As part of the integumentary system, the skin protects the newborn organism against environmental factors and serves various functions. Glucocorticoids can enter the fetal circulatory system by either elevated maternal stress perception or through therapeutic administration and are known to affect adult skin composition and wound regeneration. In the present study, we aimed at investigating the effects of local glucocorticoid administration on the process of embryonic wound healing. We performed in-ovo bead implantation of dexamethasone beads into skin incisional wounds of avian embryos and observed the local effects of the glucocorticoid on the process of skin regeneration through histology, immunohistochemistry and in-situ hybridization, using vimentin, fibronectin, E-cadherin, Dermo-1 and phospho-Histone H3 as investigational markers. Local glucocorticoid administration decelerated the healing of the skin incisional wounds by impairing mesenchymal contraction and re-epithelialization resulting in morphological changes, such as increased epithelialization and disorganized matrix formation. The results contribute to a better understanding of scarless embryonic wound healing and how glucocorticoids might interfere with the underlying molecular processes, possibly indicating that glucocorticoid therapies in prenatal clinical practice should be carefully evaluated. Full article
(This article belongs to the Special Issue Fibrosis vs Regeneration of Skin)
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11 pages, 3145 KiB  
Article
Effect of Sonic Hedgehog on the Regeneration of Epidermal Texture Patterns
by Kento Takaya, Noriko Aramaki-Hattori, Shigeki Sakai, Keisuke Okabe and Kazuo Kishi
Biomedicines 2022, 10(12), 3099; https://doi.org/10.3390/biomedicines10123099 - 1 Dec 2022
Cited by 1 | Viewed by 1124
Abstract
Wounds on embryonic mouse fetuses regenerate up to embryonic day (E) 13, but after E14, the pattern is lost and a visible scar remains. We hypothesized that the sonic hedgehog (Shh), which is involved in patterning during development, is involved in the regeneration [...] Read more.
Wounds on embryonic mouse fetuses regenerate up to embryonic day (E) 13, but after E14, the pattern is lost and a visible scar remains. We hypothesized that the sonic hedgehog (Shh), which is involved in patterning during development, is involved in the regeneration of texture. Embryos of ICR mice were surgically injured at E13, E14, and E15 and analyzed for the expression of Shh. For external Shh administration, recombinant Shh-containing slow-release beads were implanted in the wounds of mice. In contrast, cyclopamine was administered to wounds of adult mice to inhibit Shh. The expression of Shh was unaltered at E13, whereas it was upregulated in the epidermis of the wound from E14 onward. Implantation of recombinant Shh-containing beads into E13 wounds inhibited skin texture regeneration. Cyclopamine treatment inhibited epithelialization and thickening of the epidermis in the wounds of adult mice. In vitro, Shh promoted proliferation and inhibited the migration of epidermal keratinocytes through the activation of cyclin D proteins. Thus, our results suggested that the expression of Shh is involved in the regeneration of texture during wound healing, especially in epidermal keratinocyte migration and division, and could inhibit skin texture regeneration after E14. Full article
(This article belongs to the Special Issue Fibrosis vs Regeneration of Skin)
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10 pages, 4780 KiB  
Article
Downregulation of Lhx2 Markedly Impairs Wound Healing in Mouse Fetus
by Kento Takaya, Ayano Sunohara, Noriko Aramaki-Hattori, Shigeki Sakai, Keisuke Okabe and Kazuo Kishi
Biomedicines 2022, 10(9), 2132; https://doi.org/10.3390/biomedicines10092132 - 31 Aug 2022
Cited by 1 | Viewed by 1353
Abstract
Multiple transitions occur in the healing ability of the skin during embryonic development in mice. Embryos up to embryonic day 13 (E13) regenerate completely without a scar after full-thickness wounding. Then, up to E16, dermal structures can be formed, including skin appendages such [...] Read more.
Multiple transitions occur in the healing ability of the skin during embryonic development in mice. Embryos up to embryonic day 13 (E13) regenerate completely without a scar after full-thickness wounding. Then, up to E16, dermal structures can be formed, including skin appendages such as hair follicles. However, after E17, wound healing becomes incomplete, and scar formation is triggered. Lhx2 regulates the switch between maintenance and activation of hair follicle stem cells, which are involved in wound healing. Therefore, we investigated the role of Lhx2 in fetal wound healing. Embryos of ICR mice were surgically wounded at E13, E15, and E17, and the expression of Lhx2 along with mitotic (Ki67 and p63) and epidermal differentiation (keratin-10 and loricrin) markers was analyzed. The effect of Lhx2 knockdown on wound healing was observed. Lhx2 expression was not noticed in E13 due to the absence of folliculogenesis but was evident in the epidermal basal layer of E15 and E17 and at the base of E17 wounds, along with Ki67 and p63 expression. Furthermore, Lhx2 knockdown in E15 markedly prolonged wound healing and promoted clear scar formation. Therefore, Lhx2 expression is involved in cell division associated with wound healing and may contribute to scar formation in late embryos. Full article
(This article belongs to the Special Issue Fibrosis vs Regeneration of Skin)
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Review

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12 pages, 2516 KiB  
Review
Non-Healing Perianal Fistulas: A Clinical Model of Tissue Senescence Impairing Both Tissue Fibrosis and Regenerative Potential
by Jason Llaneras, Caitlyn C. Belza, Samuel Eisenstein and Marek K. Dobke
Biomedicines 2023, 11(2), 537; https://doi.org/10.3390/biomedicines11020537 - 13 Feb 2023
Viewed by 2287
Abstract
Senescent cells and fibrosis are important components that impact the regenerative capacity of skin, particularly when considering chronic non-healing wounds. Anoderm and perianal fistulas in the setting of Crohn’s disease are clinically pathophysiological extremes with consequently different healing processes which impact treatment modalities. [...] Read more.
Senescent cells and fibrosis are important components that impact the regenerative capacity of skin, particularly when considering chronic non-healing wounds. Anoderm and perianal fistulas in the setting of Crohn’s disease are clinically pathophysiological extremes with consequently different healing processes which impact treatment modalities. This study describes the implications of potential senescence reversing techniques including autologous fat grafting and pharmacologic and immunomodulating agents. Given these findings, the authors propose a future direction of study involving exosomes loaded with senolytics as a method for potentially improving chronic wound healing. In conclusion, this manuscript explores the diversity of skin healing and healing outcomes which supports the future investigation of senotherapeutic agents promoting regenerative processes for non-healing wounds. Full article
(This article belongs to the Special Issue Fibrosis vs Regeneration of Skin)
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