The role of growth factors in the pathogenesis of liver fibrosis and prospects for therapeutic impact

Kurbatova O.V.

National Medical Research Center for Children's Health of the Ministry of Health of the Russian Federation, Moscow, Russia

Liver fibrosis is a dynamic and potentially reversible process underlying chronic liver diseases and cirrhosis. It is one of the leading causes of mortality worldwide. In response to chronic injury, hepatic stellate cells (HSCs) become activated and transform into myofibroblasts. This leads to excessive synthesis and accumulation of extracellular matrix (ECM) components – collagen, fibronectin, and proteoglycans. Growth factors play a central role in this process, primarily transforming growth factor-beta (TGF-β), which is the main stimulator of fibrogenesis. Other important factors include platelet-derived growth factor (PDGF) (as a mitogen for HSCs), connective tissue growth factor (CTGF) (a mediator of TGF-β effects), and vascular endothelial growth factor (VEGF) (a stimulator of angiogenesis that enhances fibrosis). Fibrogenesis is regulated by a complex network of signaling pathways: TGF-β/Smad (central), PDGF, Wnt/β-catenin, Hedgehog, JAK-STAT, and NF-κB. Despite the deep understanding of pathogenesis, specific antifibrotic drugs do not yet exist. Elimination of the cause (etiotropic therapy) remains as the primary strategy. Promising directions for the treatment of fibrosis include: development of selective inhibitors of key pathways; combination therapy targeting multiple mechanisms simultaneously; use of regenerative medicine methods (stem cells, exosomes); personalized approaches based on biomarkers; and investigation of natural compounds (flavonoids, alkaloids) that modulate fibrotic pathways. Conclusion: growth factors, especially TGF-β, are key targets for the development of new treatments for liver fibrosis. Further research into their interactions and the creation of targeted drugs opens the way not only to halting but also to reversing fibrosis, which could significantly improve the prognosis for millions of patients.