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Updated: May 9, 2026
Ex Vivo Corneal Organ Culture Model for Wound Healing Studies
Published on: February 15, 2019
Molecular basis of organ fibrosis: potential therapeutic approaches
Asish K Ghosh1, Susan E Quaggin, Douglas E Vaughan
1Feinberg Cardiovascular Research Institute & Division of Nephrology, Northwestern University, Chicago, IL, USA. a-ghosh2@northwestern.edu
Abstract:
Fibrosis, a non-physiological wound healing in multiple organs, is associated with end-stage pathological symptoms of a wide variety of vascular injury and inflammation related diseases. In response to chemical, immunological and physical insults, the body's defense system and matrix synthetic machinery respond to healing the wound and maintain tissue homeostasis. However, uncontrolled wound healing leads to scarring or fibrosis, a pathological condition characterized by excessive synthesis and accumulation of extracellular matrix proteins, loss of tissue homeostasis and organ failure. Understanding the actual cause of pathological wound healing and identification of igniter(s) of fibrogenesis would be helpful to design novel therapeutic approaches to control pathological wound healing and to prevent fibrosis related morbidity and mortality. In this article, we review the significance of a few key cytokines (TGF-β, IFN-γ, IL-10) transcriptional activators (Sp1, Egr-1, Smad3), repressors (Smad7, Fli-1, PPAR-γ, p53, Klotho) and epigenetic modulators (acetyltransferase, methyltransferases, deacetylases, microRNAs) involved in major matrix protein collagen synthesis under pathological stage of wound healing, and the potentiality of these regulators as therapeutic targets for fibrosis treatment. The significance of endothelial to mesenchymal transition (EndMT) and senescence, two newly emerged fields in fibrosis research, has also been discussed.
Insights
Fibrosis, a pathological wound healing process, involves excessive matrix protein accumulation. Identifying key regulators like cytokines and epigenetic modulators can lead to novel therapeutic strategies for fibrosis treatment.
Area of Science:
- Cell Biology
- Pathology
- Molecular Biology
Background:
- Fibrosis is a non-physiological wound healing response seen in various organs.
- Uncontrolled healing leads to excessive extracellular matrix deposition, organ failure, and is linked to vascular injury and inflammation.
Purpose of the Study:
- To review key molecular regulators involved in pathological collagen synthesis during fibrosis.
- To explore potential therapeutic targets for treating fibrosis and preventing related mortality.
Main Methods:
- Review of literature on cytokines, transcriptional activators and repressors.
- Analysis of epigenetic modulators and their role in collagen synthesis.
- Discussion of endothelial to mesenchymal transition (EndMT) and senescence in fibrosis.
Main Results:
- Identified key cytokines (TGF-β, IFN-γ, IL-10), activators (Sp1, Egr-1, Smad3), and repressors (Smad7, Fli-1, PPAR-γ, p53, Klotho) in pathological collagen synthesis.
- Highlighted the role of epigenetic modulators (acetyltransferases, methyltransferases, deacetylases, microRNAs) in matrix protein synthesis.
- Emphasized the emerging significance of EndMT and senescence in fibrotic processes.
Conclusions:
- Understanding the molecular mechanisms of fibrogenesis is crucial for developing effective anti-fibrotic therapies.
- Key cytokines, transcriptional regulators, and epigenetic factors represent promising therapeutic targets for fibrosis.
- EndMT and senescence are critical areas for future research in fibrosis treatment.
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