Fibroblasts: Insights from Molecular and Pathophysiology Perspectives

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: closed (15 July 2024) | Viewed by 4864

Special Issue Editors

Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland
Interests: fibroblasts into myofibroblasts (FMT); epithelial-mesenchymal transition (EMT); endothelial-mesenchymal transition (EndMT); asthma and others fibrosis-related diseases
Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland
Interests: fibroblast; fibroblast to myofibroblast transition (FMT); fibrotic diseases and bronchial asthma; fibrosis

Special Issue Information

Dear Colleagues,

Fibroblasts are spindle-shaped connective tissue cells found in the interstitial spaces of many organs (skin, heart, lungs, skeletal muscle). They are mainly responsible for the production of extracellular matrix (ECM) to form connective tissue by producing and secreting into the extracellular space many types of extracellular matrix proteins.

Fibroblasts are also capable of active remodelling the microstructure of the ECM through covalent cross-linking, protein glycosylation and controlled proteolysis, which occurs through the balanced secretion of ECM-modifying enzymes e.g. matrix metalloproteinases (MMPs) and their inhibitors (TIMPs). They are also a source of many pro-inflammatory and anti-inflammatory cytokines, growth factors and chemotactic factors. The secretory activity of fibroblasts varies depending on the state of the tissue or organ. Fibroblasts are also responsible for tissue biomechanics by generating mechanical forces at the tissue level, which also contributes to tissue-specific matrix formation and maintenance of tissue-specific biomechanics.

We are pleased to introduce to you the new Special Issue of the Biomedicines entitled: “Fibroblasts: Insights from Molecular and Pathophysiology Perspectives”.

Better understanding of the nature of fibroblasts and their phenotypic switches underlying the fibrosis-related diseases may become a milestone in the searching for novel, efficient and personalized treatment strategies of many diseases. Therefore, this Special Issue aims to present the current advances in our understanding of all aspects of fibroblasts biology and functions in physiology and pathological processes. We invite you to contribute to a special issue on fibroblasts, both in the context of the development of new research models, their differentiation and de-differentiation (for regeneration medicine), and the role of fibroblasts in physiological states, pathology and tumorigenesis.

Dr. Milena Paw
Dr. Dawid Wnuk
Guest Editors

Manuscript Submission Information

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Keywords

  • fibroblasts and myofibroblasts
  • fibrosis (organ and tissue fibrosis)
  • tissue remodelling
  • extracellular matrix
  • cellular signalling
  • fibroblast differentiation
  • new in vitro models of fibrotic-related diseases

Published Papers (3 papers)

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Research

14 pages, 4294 KiB  
Article
BRD3 Regulates the Inflammatory and Stress Response in Rheumatoid Arthritis Synovial Fibroblasts
by Tanja Seifritz, Matthias Brunner, Eva Camarillo Retamosa, Malgorzata Maciukiewicz, Monika Krošel, Larissa Moser, Thomas Züllig, Matija Tomšič, Oliver Distler, Caroline Ospelt and Kerstin Klein
Biomedicines 2023, 11(12), 3188; https://doi.org/10.3390/biomedicines11123188 - 30 Nov 2023
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Abstract
Background: Individual functions of members of the bromodomain (BRD) and extra-terminal (BET) protein family underlying the anti-inflammatory effects of BET inhibitors in rheumatoid arthritis (RA) are incompletely understood. Here, we aimed to analyze the regulatory functions of BRD3, an understudied member of the [...] Read more.
Background: Individual functions of members of the bromodomain (BRD) and extra-terminal (BET) protein family underlying the anti-inflammatory effects of BET inhibitors in rheumatoid arthritis (RA) are incompletely understood. Here, we aimed to analyze the regulatory functions of BRD3, an understudied member of the BET protein family, in RA synovial fibroblasts (FLS). Methods: BRD3 was silenced in FLS prior to stimulation with TNF. Alternatively, FLS were treated with I-BET. Transcriptomes were analyzed by RNA sequencing (RNAseq), followed by pathway enrichment analysis. We confirmed results for selective target genes by real-time PCR, ELISA, and Western blotting. Results: BRD3 regulates the expression of several cytokines and chemokines in FLS, and positively correlates with inflammatory scores in the RA synovium. In addition, RNAseq pointed to a profound role of BRD3 in regulating FLS proliferation, metabolic adaption, and response to stress, including oxidative stress, and autophagy. Conclusions: BRD3 acts as an upstream regulatory factor that integrates the response to inflammatory stimuli and stress conditions in FLS and executes many functions of BET proteins that have previously been identified using pan-BET inhibitors. Full article
(This article belongs to the Special Issue Fibroblasts: Insights from Molecular and Pathophysiology Perspectives)
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14 pages, 2202 KiB  
Article
Is Spheroid a Relevant Model to Address Fibrogenesis in Keloid Research?
by Zélie Dirand, Marion Tissot, Brice Chatelain, Céline Viennet and Gwenaël Rolin
Biomedicines 2023, 11(9), 2350; https://doi.org/10.3390/biomedicines11092350 - 23 Aug 2023
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Abstract
Keloid refers to a fibro-proliferative disorder characterized by an accumulation of extracellular matrix at the dermis level, overgrowing beyond the initial wound and forming tumor-like nodule areas. The absence of treatment for keloid is clearly related to limited knowledge about keloid etiology. In [...] Read more.
Keloid refers to a fibro-proliferative disorder characterized by an accumulation of extracellular matrix at the dermis level, overgrowing beyond the initial wound and forming tumor-like nodule areas. The absence of treatment for keloid is clearly related to limited knowledge about keloid etiology. In vitro, keloids were classically studied through fibroblasts monolayer culture, far from keloid in vivo complexity. Today, cell aggregates cultured as 3D spheroid have gained in popularity as new tools to mimic tissue in vitro. However, no previously published works on spheroids have specifically focused on keloids yet. Thus, we hypothesized that spheroids made of keloid fibroblasts (KFs) could be used to model fibrogenesis in vitro. Our objective was to qualify spheroids made from KFs and cultured in a basal or pro-fibrotic environment (+TGF-β1). As major parameters for fibrogenesis assessment, we evaluated apoptosis, myofibroblast differentiation and response to TGF-β1, extracellular matrix (ECM) synthesis, and ECM-related genes regulation in KFs spheroids. We surprisingly observed that fibrogenic features of KFs are strongly downregulated when cells are cultured in 3D. In conclusion, we believe that spheroid is not the most appropriate model to address fibrogenesis in keloid, but it constitutes an efficient model to study the deactivation of fibrotic cells. Full article
(This article belongs to the Special Issue Fibroblasts: Insights from Molecular and Pathophysiology Perspectives)
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14 pages, 2691 KiB  
Article
Bronchial Fibroblasts from Asthmatic Patients Display Impaired Responsiveness to Direct Current Electric Fields (dcEFs)
by Anastasiia Pavlenko, Sławomir Lasota, Dawid Wnuk, Milena Paw, Jarosław Czyż, Marta Michalik and Zbigniew Madeja
Biomedicines 2023, 11(8), 2138; https://doi.org/10.3390/biomedicines11082138 - 29 Jul 2023
Cited by 1 | Viewed by 1177
Abstract
Accumulating evidence suggests that an important role is played by electric signals in modifying cell behaviour during developmental, regenerative and pathological processes. However, their role in asthma has not yet been addressed. Bronchial fibroblasts have recently been identified having important roles in asthma [...] Read more.
Accumulating evidence suggests that an important role is played by electric signals in modifying cell behaviour during developmental, regenerative and pathological processes. However, their role in asthma has not yet been addressed. Bronchial fibroblasts have recently been identified having important roles in asthma development. Therefore, we adapted an experimental approach based on the lineages of human bronchial fibroblasts (HBF) derived from non-asthmatic (NA) donors and asthmatic (AS) patients to elucidate whether their reactivity to direct current electric fields (dcEF) could participate in the asthmatic process. The efficient responsiveness of NA HBF to an electric field in the range of 2–4 V/cm was illustrated based on the perpendicular orientation of long axes of the cells to the field lines and their directional movement towards the anode. These responses were related to the activity of TGF-β signalling, as the electrotaxis and re-orientation of NA HBF polarity was impaired by the inhibitors of canonical and non-canonical TGF-β-dependent pathways. A similar tendency towards perpendicular cell-dcEF orientation was observed for AS HBF. However, their motility remained insensitive to the electric field applied at 2–4 V/cm. Collectively, these observations demonstrate the sensitivity of NA HBF to dcEF, as well as the inter-relations between this parameter and the canonical and non-canonical TGF-β pathways, and the differences between the electrotactic responses of NA and AS HBF point to the possible role of their dcEFs in desensitisation in the asthmatic process. This process may impair the physiologic behaviour of AS HBF functions, including cell motility, ECM deposition, and contractility, thus promoting bronchial wall remodelling, which is a characteristic of bronchial asthma. Full article
(This article belongs to the Special Issue Fibroblasts: Insights from Molecular and Pathophysiology Perspectives)
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