Organ Fibrosis: From Molecular Mechanisms to Clinical Therapies

Topic Information

Dear Colleagues, 

Fibrosis is a dynamic process which is mainly characterized by an excessive accumulation of extracellular matrices. Fibrosis generally occurs as an uncontrolled wound-healing response to multiple and chronic injuries. It induces the alteration of organ architecture and leads to loss of organ function. Fibrosis is a pathology that affects several organs, such as the kidney, lungs, liver, skin, peritoneum, and heart. In addition, even if the main source of the extracellular matrix is activated by myofibroblasts, many cell types modulate the phenomenon (epithelial and mesothelial cells, endothelial cells, pericytes, vascular smooth muscle cells, inflammatory cells, and mesenchymal stem cells). Commonly, the fibrotic process is initiated by parenchymal damage, followed by unsolved inflammation; thus, some molecular mechanisms at the origin of fibrosis are shared by different organs. In this scenario, additional tissue-specific mechanisms are responsible for fibrosis. Keeping in mind that in certain situations, fibrosis could be a reversible process, deeper knowledge of its foundation is highly necessary in order to develop new therapeutic strategies. The aim of this Topic is to report new findings that advance knowledge of the molecular mechanisms and clinical therapies of organ fibrosis. We welcome submissions of research papers and reviews that focus on aspects of known mechanisms/pathways/clinical therapies, such as epithelial–mesenchymal transition, TGF-beta signaling, myofibroblast activation, proliferation, and senescence, but also manuscripts that explore new aspects.

Dr. Maurizio Onisto
Dr. Valentina Masola
Topic Editors

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Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Biology biology	3.6	5.7	2012	16.4 Days	CHF 2700
Biomolecules biomolecules	4.8	9.4	2011	18.4 Days	CHF 2700
Cells cells	5.1	9.9	2012	17 Days	CHF 2700
Journal of Clinical Medicine jcm	3.0	5.7	2012	16 Days	CHF 2600
Organoids organoids	-	-	2022	19.3 Days	CHF 1000

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Published Papers (3 papers)

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18 pages, 7116 KiB  

Open AccessArticle

High Glucose Levels Promote Switch to Synthetic Vascular Smooth Muscle Cells via Lactate/GPR81

by Jing Yang, Glenn R. Gourley, Adam Gilbertsen, Chi Chen, Lei Wang, Karen Smith, Marion Namenwirth and Libang Yang

Cells 2024, 13(3), 236; https://doi.org/10.3390/cells13030236 - 26 Jan 2024

Cited by 5 | Viewed by 2938

Abstract

Hyperglycemia, lipotoxicity, and insulin resistance are known to increase the secretion of extracellular matrix from cardiac fibroblasts as well as the activation of paracrine signaling from cardiomyocytes, immune cells, and vascular cells, which release fibroblast-activating mediators. However, their influences on vascular smooth muscle [...] Read more.

Hyperglycemia, lipotoxicity, and insulin resistance are known to increase the secretion of extracellular matrix from cardiac fibroblasts as well as the activation of paracrine signaling from cardiomyocytes, immune cells, and vascular cells, which release fibroblast-activating mediators. However, their influences on vascular smooth muscle cells (vSMCs) have not been well examined. This study aimed to investigate whether contractile vascular vSMCs could develop a more synthetic phenotype in response to hyperglycemia. The results showed that contractile and synthetic vSMCs consumed high glucose in different ways. Lactate/GPR81 promotes the synthetic phenotype in vSMCs in response to high glucose levels. The stimulation of high glucose was associated with a significant increase in fibroblast-like features: synthetic vSMC marker expression, collagen 1 production, proliferation, and migration. GPR81 expression is higher in blood vessels in diabetic patients and in the high-glucose, high-lipid diet mouse. The results demonstrate that vSMCs assume a more synthetic phenotype when cultured in the presence of high glucose and, consequently, that the high glucose could trigger a vSMC-dependent cardiovascular disease mechanism in diabetes via lactate/GPR81. Full article

(This article belongs to the Topic Organ Fibrosis: From Molecular Mechanisms to Clinical Therapies)

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20 pages, 1387 KiB  

Open AccessReview

Fibroblast Activation Protein Alpha (FAPα) in Fibrosis: Beyond a Perspective Marker for Activated Stromal Cells?

by Nataliya Basalova, Natalya Alexandrushkina, Olga Grigorieva, Maria Kulebyakina and Anastasia Efimenko

Biomolecules 2023, 13(12), 1718; https://doi.org/10.3390/biom13121718 - 29 Nov 2023

Cited by 12 | Viewed by 3967

Abstract

The development of tissue fibrosis is a complex process involving the interaction of multiple cell types, which makes the search for antifibrotic agents rather challenging. So far, myofibroblasts have been considered the key cell type that mediated the development of fibrosis and thus [...] Read more.

The development of tissue fibrosis is a complex process involving the interaction of multiple cell types, which makes the search for antifibrotic agents rather challenging. So far, myofibroblasts have been considered the key cell type that mediated the development of fibrosis and thus was the main target for therapy. However, current strategies aimed at inhibiting myofibroblast function or eliminating them fail to demonstrate sufficient effectiveness in clinical practice. Therefore, today, there is an unmet need to search for more reliable cellular targets to contribute to fibrosis resolution or the inhibition of its progression. Activated stromal cells, capable of active proliferation and invasive growth into healthy tissue, appear to be such a target population due to their more accessible localization in the tissue and their high susceptibility to various regulatory signals. This subpopulation is marked by fibroblast activation protein alpha (FAPα). For a long time, FAPα was considered exclusively a marker of cancer-associated fibroblasts. However, accumulating data are emerging on the diverse functions of FAPα, which suggests that this protein is not only a marker but also plays an important role in fibrosis development and progression. This review aims to summarize the current data on the expression, regulation, and function of FAPα regarding fibrosis development and identify promising advances in the area. Full article

(This article belongs to the Topic Organ Fibrosis: From Molecular Mechanisms to Clinical Therapies)

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17 pages, 19577 KiB  

Open AccessArticle

Sja-Let-7 Attenuates Carbon Tetrachloride-Induced Liver Fibrosis in a Mouse Model via Col1α2

by Haoran Zhong, Bowen Dong, Danlin Zhu, Hao Li, Ke Lu, Zhiqiang Fu, Jinming Liu and Yamei Jin

Biology 2023, 12(12), 1465; https://doi.org/10.3390/biology12121465 - 24 Nov 2023

Cited by 3 | Viewed by 1901

Abstract

Liver fibrosis (LF) is a chronic progressive disease with no definitive treatment. The aim of this study was to assess helminth-derived molecules as potential therapeutic targets to prevent or reverse LF. A mouse model of carbon tetrachloride (CCL₄)-induced LF was established [...] Read more.

Liver fibrosis (LF) is a chronic progressive disease with no definitive treatment. The aim of this study was to assess helminth-derived molecules as potential therapeutic targets to prevent or reverse LF. A mouse model of carbon tetrachloride (CCL₄)-induced LF was established and sja-let-7 was overexpressed by treatment with a miRNA agomir once per week. After four weeks, serum biochemistry, hepatic hydroxyproline content measurements, liver histology, mRNA expression profiling of fibrotic markers, the dual-luciferase reporter assay, and fluorescence in situ hybridization (FISH) were performed. Administration of the sja-let-7 agomir markedly ameliorated hepatosplenomegaly and reduced the liver hydroxyproline content. Liver histological analysis showed significant reductions in collagen deposition in the sja-let-7 agomir-treated mice. Additionally, the mRNA levels of both pro-fibrotic markers and pro-inflammatory cytokines were diminished after treatment. Furthermore, the dual-luciferase reporter assay and FISH identified the α2 chain of collagen type 1 (Col1α2) as the direct target of sja-let-7. Accordingly, the progression of LF was attenuated by targeting Col1α2 and the TGF-β/Smad signaling pathway. Full article

(This article belongs to the Topic Organ Fibrosis: From Molecular Mechanisms to Clinical Therapies)

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