Fibrosis-related signaling pathways

Fibrosis-related signaling pathways represent a broad category of interconnected molecular cascades that orchestrate the pathological accumulation of extracellular matrix (ECM) in response to chronic injury. The most prominent of these is the Transforming Growth Factor-beta (TGF-beta) pathway, which acts as a master regulator of myofibroblast differentiation and collagen synthesis [1]. Other critical pathways include Wnt/beta-catenin, Notch, and Hedgehog, which contribute to cell proliferation, survival, and the epithelial-mesenchymal transition (EMT) [2]. These pathways are essential for normal wound healing but become aberrantly persistent in chronic diseases, leading to organ scarring and failure. Therapeutic intervention typically targets specific nodes within these pathways, such as receptor tyrosine kinases or specific ligands, to mitigate fibrotic progression [3]. Because these pathways are involved in numerous homeostatic processes, achieving therapeutic efficacy without significant side effects remains a major challenge in drug development. [1] Meng, X. M., et al. (2016). Nature Reviews Nephrology. [2] Hu, B., & Phan, S. H. (2013). Current Opinion in Rheumatology. [3] Richeldi, L., et al. (2014). New England Journal of Medicine.

Other names

Fibrotic signaling cascadesFibrogenesis pathwaysTGF-beta/SMAD signaling pathwayWnt/beta-catenin signalingNotch signaling pathwayHedgehog signaling pathway

Inhibition of growth factor receptors (e.g., VEGFR, PDGFR, FGFR), blockade of pro-fibrotic ligands like TGF-beta or CTGF, and modulation of downstream intracellular signaling cascades to inhibit myofibroblast activation.