Skip to main content

Fibrosis: from mechanisms to novel treatments

Fibrosis is a pathological hallmark in the majority of chronic inflammatory ailments, characterized by the excessive accumulation of extracellular matrix (ECM) components, including collagen and fibronectin. The etiology of fibrosis is diverse, encompassing hereditary inflammatory disorders, persistent infections, repeated exposure to toxins, irritants, and smoke, autoimmune inflammation, and rejection in transplantation. A shared characteristic in these fibrotic diseases is the activation of ECM-producing myofibroblasts, a central player in the remodeling of fibrotic tissue. Collagen deposition is a crucial and typically reversible facet of wound healing, severe or recurrent tissue injuries, or dysregulation in wound healing, it is necessary for the progression of normal tissue repair into an irreversible fibrotic state.

Gastrointestinal fibrosis is characterized as a state of heightened biological entropy resulting from aberrant tissue repair reactions. Acute or chronic inflammation in the gastrointestinal tract, notably in conditions such as inflammatory bowel disease, particularly Crohn’s disease, triggers fibrosis and stricture, often necessitating surgical or endoscopic intervention. Myocardial infarction, elevated serum cholesterol, obesity, poorly managed diabetes, and hypertension also contribute to fibrosis in various cases, with chronic inflammation playing a pivotal role in most instances.

This special edition centers on gastrointestinal fibrosis (Dr. Mikami’s article) and cardiac fibrosis (Dr. Ieda’s article), aiming to disseminate information on recent developments in fibrosis and its therapeutic approaches.

Dr. Mikami delves into the contemporary understanding of the pathogenesis of gastrointestinal fibrosis, concentrating on Crohn’s disease and fibrosis arising from stenosis post-endoscopic submucosal dissection (ESD). The article addresses significant challenges in developing antifibrotic agents and highlights key fibrotic pathways that have progressed to clinical trials [1].

The incidence of heart disease in Japan is on the rise due to lifestyle westernization and an aging population. Regenerative medicine emerges as a promising treatment option when conventional therapies are inadequate. However, stem cell limitations have prompted the exploration of “direct myocardial initialization” as an alternative treatment. Myocardial regeneration involves the in situ trans-differentiation of cardiac fibroblasts into cardiomyocytes. Dr. Ieda and collaborators have identified that three cardiomyogenic transcription factors, Gata4, Mef2c, and Tbx5 (GMT), can directly reprogram fibroblasts into induced cardiomyocytes (iCM) in mice. In humans, additional factors such as Mesp1 and Myocd are required. The article outlines factors that inhibit or promote reprogramming, with ongoing improvements for human applications, paving the way for further advancements in cardiac initialization research [2].


  1. Iwata K, Mikami Y, Kato M, Yahagi N, Kanai T. Pathogenesis and management of gastrointestinal inflammation and fibrosis: from inflammatory bowel diseases to endoscopic surgery. Inflamm Regen. 2021;41(1):21.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Yamakawa H, Ieda M. Cardiac regeneration by direct reprogramming in this decade and beyond. Inflamm Regen. 2021;41(1):20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations



The author(s) read and approved the final manuscript.

Corresponding author

Correspondence to Akihiko Yoshimura.

Ethics declarations

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yoshimura, A. Fibrosis: from mechanisms to novel treatments. Inflamm Regener 44, 1 (2024).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: