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Decoding fibroblast activation: Transcriptional networks in hepatic stellate cells and across fibrotic organs (Review).

Created on 21 Aug 2026

Authors

Denita Charoenthanakitkul, Chaiyaboot Ariyachet

Published in

International journal of molecular medicine. Volume 58. Issue 4. Epub Aug 21, 2026.

Abstract

Fibrosis is a progressive pathological process characterized by excessive extracellular matrix (ECM) deposition and structural remodeling that ultimately leads to organ dysfunction. In organs such as the liver, lung, heart and kidney, sustained activation of fibroblasts and their differentiation into myofibroblasts are key drivers of fibrotic progression. Growing evidence suggests that these cellular transitions are regulated by intricate transcriptional networks that integrate inflammatory, metabolic and mechanical signals. Liver fibrosis provides a well‑established framework for studying the transcriptional regulation of fibroblast activation, largely driven by the differentiation of hepatic stellate cells (HSCs) into collagen‑secreting myofibroblasts. Various transcription factors coordinate major signaling pathways to regulate fibroblast proliferation, ECM production and cell survival. These transcriptional programs not only sustain fibrogenesis but also influence whether fibrotic responses resolve or progress to chronic tissue scarring. In the present review, current advances in understanding transcriptional regulatory networks governing fibroblast activation were summarized, with a primary focus on HSCs while highlighting shared mechanisms across multiple fibrotic organs. Emerging therapeutic strategies targeting transcription factors and their upstream regulatory pathways were further discussed. A deeper understanding of these transcriptional circuits may facilitate the development of novel antifibrotic therapies and enhance strategies for resolving fibrosis in various organs.

PMID:
42627051
Bibliographic data and abstract were imported from PubMed on 21 Aug 2026.

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