Cellular and Molecular Mechanisms of Organ Fibrosis

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

Deadline for manuscript submissions: closed (15 January 2024) | Viewed by 4810

Special Issue Editors


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Guest Editor
Department of Life Sciences, Manchester Metropolitan University, Manchester, UK
Interests: organ fibrosis; molecular biology; developmental biology; cell biology

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Guest Editor
Wellcome Centre for Cell-Matrix Research, Faculty of Biology, Medicine & Health, University of Manchester, Oxford Road, Manchester M13 9PL, UK
Interests: fibrosis of the liver; lung, kidney and heart; anti-fibrotic therapies; fibrosis biomarkers

Special Issue Information

Dear Colleagues,

Organ fibrosis is a complex process driven by numerous cell types and molecular processes. The key characteristic of fibrosis is the dysregulation of the extracellular matrix (ECM) that causes altered tissue structure and impaired organ function. Despite great progress being made in understanding the complex cell and molecular mechanisms which drive fibrosis, treatment options remain limited.

Fibrotic ECM is produced primarily by cells referred to as myofibroblasts, or myofibroblast-like cells. Recent advances in single-cell and spatial transcriptomics have highlighted the heterogeneity that exists within myofibroblast cell populations and within their quiescent precursor populations in unprecedented detail. At the same time, proteomics data are revealing more about the changes that occur within the ECM during fibrosis and linking this to the mechano-sensing pathways that contribute to fibrosis.

Though our understanding of the composition of myofibroblast populations and their surrounding environment has increased, our mechanistic understanding of how each of these sub-populations respond distinctly to injury remains incomplete. Several of these cell types have phenotypic similarities with counterparts in different organs and respond similarly to central cues such as TGFb signaling and organ stiffening. However, several sub-populations of myofibroblasts appear to show distinct transcriptomic profiles which suggest bespoke roles in coordinating the response to injury, regeneration, and scar formation.

In this Special Issue, we invite submissions which build upon our current understanding of the processes that drive organ fibrosis with original research articles as well as reviews of the current state of this compelling area of research.

Dr. James Pritchett
Dr. Elliot Jokl
Guest Editors

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Keywords

  • fibrosis
  • scarring
  • regeneration
  • myofibroblast
  • extracellular matrix

Published Papers (3 papers)

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Review

20 pages, 3888 KiB  
Review
Scarring and Skin Fibrosis Reversal with Regenerative Surgery and Stem Cell Therapy
by Aurora Almadori and Peter EM Butler
Cells 2024, 13(5), 443; https://doi.org/10.3390/cells13050443 - 3 Mar 2024
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Abstract
Skin scarring and fibrosis affect millions of people worldwide, representing a serious clinical problem causing physical and psychological challenges for patients. Stem cell therapy and regenerative surgery represent a new area of treatment focused on promoting the body’s natural ability to repair damaged [...] Read more.
Skin scarring and fibrosis affect millions of people worldwide, representing a serious clinical problem causing physical and psychological challenges for patients. Stem cell therapy and regenerative surgery represent a new area of treatment focused on promoting the body’s natural ability to repair damaged tissue. Adipose-derived stem cells (ASCs) represent an optimal choice for practical regenerative medicine due to their abundance, autologous tissue origin, non-immunogenicity, and ease of access with minimal morbidity for patients. This review of the literature explores the current body of evidence around the use of ASCs-based regenerative strategies for the treatment of scarring and skin fibrosis, exploring the different surgical approaches and their application in multiple fibrotic skin conditions. Human, animal, and in vitro studies demonstrate that ASCs present potentialities in modifying scar tissue and fibrosis by suppressing extracellular matrix (ECM) synthesis and promoting the degradation of their constituents. Through softening skin fibrosis, function and overall quality of life may be considerably enhanced in different patient cohorts presenting with scar-related symptoms. The use of stem cell therapies for skin scar repair and regeneration represents a paradigm shift, offering potential alternative therapeutic avenues for fibrosis, a condition that currently lacks a cure. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Organ Fibrosis)
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17 pages, 2487 KiB  
Review
Exploring Extracellular Matrix Crosslinking as a Therapeutic Approach to Fibrosis
by Sarah M. Lloyd and Yupeng He
Cells 2024, 13(5), 438; https://doi.org/10.3390/cells13050438 - 2 Mar 2024
Viewed by 1306
Abstract
The extracellular matrix (ECM) provides structural support for tissues and regulatory signals for resident cells. ECM requires a careful balance between protein accumulation and degradation for homeostasis. Disruption of this balance can lead to pathological processes such as fibrosis in organs across the [...] Read more.
The extracellular matrix (ECM) provides structural support for tissues and regulatory signals for resident cells. ECM requires a careful balance between protein accumulation and degradation for homeostasis. Disruption of this balance can lead to pathological processes such as fibrosis in organs across the body. Post-translational crosslinking modifications to ECM proteins such as collagens alter ECM structure and function. Dysregulation of crosslinking enzymes as well as changes in crosslinking composition are prevalent in fibrosis. Because of the crucial roles these ECM crosslinking pathways play in disease, the enzymes that govern crosslinking events are being explored as therapeutic targets for fibrosis. Here, we review in depth the molecular mechanisms underlying ECM crosslinking, how ECM crosslinking contributes to fibrosis, and the therapeutic strategies being explored to target ECM crosslinking in fibrosis to restore normal tissue structure and function. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Organ Fibrosis)
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26 pages, 2500 KiB  
Review
Potential of Plant-Derived Compounds in Preventing and Reversing Organ Fibrosis and the Underlying Mechanisms
by Patrícia dos Santos Azeredo, Daping Fan, E. Angela Murphy and Wayne E. Carver
Cells 2024, 13(5), 421; https://doi.org/10.3390/cells13050421 - 28 Feb 2024
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Abstract
Increased production of extracellular matrix is a necessary response to tissue damage and stress. In a normal healing process, the increase in extracellular matrix is transient. In some instances; however, the increase in extracellular matrix can persist as fibrosis, leading to deleterious alterations [...] Read more.
Increased production of extracellular matrix is a necessary response to tissue damage and stress. In a normal healing process, the increase in extracellular matrix is transient. In some instances; however, the increase in extracellular matrix can persist as fibrosis, leading to deleterious alterations in organ structure, biomechanical properties, and function. Indeed, fibrosis is now appreciated to be an important cause of mortality and morbidity. Extensive research has illustrated that fibrosis can be slowed, arrested or even reversed; however, few drugs have been approved specifically for anti-fibrotic treatment. This is in part due to the complex pathways responsible for fibrogenesis and the undesirable side effects of drugs targeting these pathways. Natural products have been utilized for thousands of years as a major component of traditional medicine and currently account for almost one-third of drugs used clinically worldwide. A variety of plant-derived compounds have been demonstrated to have preventative or even reversal effects on fibrosis. This review will discuss the effects and the underlying mechanisms of some of the major plant-derived compounds that have been identified to impact fibrosis. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Organ Fibrosis)
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