Profibrotic Mediators in Hypertrophic Scarring

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Tissues and Organs".

Deadline for manuscript submissions: closed (15 June 2023) | Viewed by 2525

Special Issue Editor

Department of Surgery, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB, Canada
Interests: wound healing; Hypertrophic scars; Cytokines; Burns

Special Issue Information

Dear Colleagues, 

The process and mechanism of physiological skin wound healing have been extensively studied and are well understood. However, the complications caused by abnormal wound healing, such as chronic wounds,unhealing wounds, and scar or keloid formation have not been effectively prevented and treated, which are still the medical problems that endanger people's body and psychological health, and pose a significant medical expense every year. As a common complication of burns, hypertrophic scars result from fibrotic wound healing after burn injuries. Both cellular and molecular aspects participate in fibrotic wound healing. Given the extracellular matrix-rich structure of the skin, comprehensive study on structural protein molecules, growth factors, chemokines, as well as other cytokines may be an important breakthrough to find the profibrotic mediators, which construct a fibrotic microenvironment, together with cells, contributing to hypertrophic scarring. Exploring an effective therapeutic strategy on hypertrophic scars is necessary to improve people’s health and life quality. We welcome your submissions of original research and review articles with this specific topic.

Therefore, welcome to contribute this Special Issue.

Dr. Jie Ding
Guest Editor

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Keywords

  • fibrotic wound healing
  • hypertrophic scars
  • profibrotic mediators

Published Papers (2 papers)

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Research

18 pages, 7044 KiB  
Article
Slow Interstitial Fluid Flow Activates TGF-β Signaling and Drives Fibrotic Responses in Human Tenon Fibroblasts
by Cornelius Jakob Wiedenmann, Charlotte Gottwald, Kosovare Zeqiri, Janne Frömmichen, Emma Bungert, Moritz Gläser, Jeanne Ströble, Robert Lohmüller, Thomas Reinhard, Jan Lübke and Günther Schlunck
Cells 2023, 12(17), 2205; https://doi.org/10.3390/cells12172205 - 04 Sep 2023
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Abstract
Background: Fibrosis limits the success of filtering glaucoma surgery. We employed 2D and 3D in vitro models to assess the effects of fluid flow on human tenon fibroblasts (HTF). Methods: HTF were exposed to continuous or pulsatile fluid flow for 48 or 72 [...] Read more.
Background: Fibrosis limits the success of filtering glaucoma surgery. We employed 2D and 3D in vitro models to assess the effects of fluid flow on human tenon fibroblasts (HTF). Methods: HTF were exposed to continuous or pulsatile fluid flow for 48 or 72 h, at rates expected at the transscleral outflow site after filtering surgery. In the 2D model, the F-actin cytoskeleton and fibronectin 1 (FN1) were visualized by confocal immunofluorescence microscopy. In the 3D model, mRNA and whole cell lysates were extracted to analyze the expression of fibrosis-associated genes by qPCR and Western blot. The effects of a small-molecule inhibitor of the TGF-β receptor ALK5 were studied. Results: Slow, continuous fluid flow induced fibrotic responses in the 2D and 3D models. It elicited changes in cell shape, the F-actin cytoskeleton, the deposition of FN1 and activated the intracellular TGF-β signaling pathway to induce expression of fibrosis-related genes, such as CTGF, FN1 and COL1A1. ALK5-inhibition reduced this effect. Intermittent fluid flow also induced fibrotic changes, which decreased with increasing pause duration. Conclusions: Slow interstitial fluid flow is sufficient to induce fibrosis, could underlie the intractable nature of fibrosis following filtering glaucoma surgery and might be a target for antifibrotic therapy. Full article
(This article belongs to the Special Issue Profibrotic Mediators in Hypertrophic Scarring)
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18 pages, 7765 KiB  
Article
Characteristics of Serum Exosomes after Burn Injury and Dermal Fibroblast Regulation by Exosomes In Vitro
by Jie Ding, Yingying Pan, Shammy Raj, Lindy Schaffrick, Jolene Wong, Antoinette Nguyen, Sharada Manchikanti, Larry Unsworth, Peter Kwan and Edward Tredget
Cells 2023, 12(13), 1738; https://doi.org/10.3390/cells12131738 - 28 Jun 2023
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Abstract
(1) Background: Exosomes (EXOs) have been considered a new target thought to be involved in and treat wound healing. More research is needed to fully understand EXO characteristics and the mechanisms of EXO-mediated wound healing, especially wound healing after burn injury. (2) Methods: [...] Read more.
(1) Background: Exosomes (EXOs) have been considered a new target thought to be involved in and treat wound healing. More research is needed to fully understand EXO characteristics and the mechanisms of EXO-mediated wound healing, especially wound healing after burn injury. (2) Methods: All EXOs were isolated from 85 serum samples of 29 burn patients and 13 healthy individuals. We characterized the EXOs for morphology and density, serum concentration, protein level, marker expression, size distribution, and cytokine content. After a confirmation of EXO uptake by dermal fibroblasts, we also explored the functional regulation of primary human normal skin and hypertrophic scar fibroblast cell lines by the EXOs in vitro, including cell proliferation and apoptosis. (3) Results: EXOs dynamically changed their morphology, density, size, and cytokine level during wound healing in burn patients, which were correlated with burn severity and the stages of wound healing. EXOs both from burn patients and healthy individuals stimulated dermal fibroblast proliferation and apoptosis. (4) Conclusions: EXO features may be important signals that influence wound healing after burn injury; however, to understand the mechanisms by which EXOs regulates the fibroblasts in healing wounds, further studies will be required. Full article
(This article belongs to the Special Issue Profibrotic Mediators in Hypertrophic Scarring)
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