【摘 要】
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Liver fibrosis is a life-threatening disease, with challenging morbidity and mortality for healthcare systems worldwide. It imparts an enormous economic burden to societies, mak-ing continuous research and informational updates about its pathogenesis and
【机 构】
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Department of Pharmacology and Biochemistry,Faculty of Dental Medicine and Health Osijek,J.J.Strossm
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Liver fibrosis is a life-threatening disease, with challenging morbidity and mortality for healthcare systems worldwide. It imparts an enormous economic burden to societies, mak-ing continuous research and informational updates about its pathogenesis and treatment crucial. This review′s focus is on the current knowledge about the Wnt signaling path-way, serving as an important pathway in liver fibrosis de-velopment and activation of hepatic stellate cells (HSCs). Two types of Wnt pathways are distinguished, namely the ?-catenin-dependent canonical and non-canonical Ca2+ or planar cell polarity (PCP)-dependent pathway. The dynam-ic balance of physiologically healthy liver and hepatocytes is disturbed by repeated liver injuries. Activation of the ?-catenin Wnt pathway prevents the regeneration of hepato-cytes by the replacement of extracellular matrix (ECM), leading to the appearance of scar tissue and the formation of regenerated nodular hepatocytes, lacking the original function of healthy hepatocytes. Therefore, liver function is reduced due to the severely advanced disease. Selec-tive inhibition of ?-catenin inhibits inflammatory processes (since chemokines and pro-inflammatory cytokines are produced during Wnt activation), reduces growth of acti-vated HSCs and reduces collagen synthesis and angiogen-esis, thereby reducing the progression of liver fibrosis in vivo. While the canonical Wnt pathway is usually inactive in a physiologically healthy liver, it shows activity during cell regeneration or renewal and in certain pathophysiolog-ical conditions, such as liver diseases and cancer. Targeted blocking of some of the basic components of the Wnt path-way is a therapeutic approach. These include the frizzled transmembrane receptor (Fz) receptors using the secreted frizzled-related protein family (sFRP), Fz-coreceptors low-density LRP 5/6 through dickkopf-related protein 1 (DKK1) or niclosamide, glycogen kinase-3 beta (GSK-3β) using SB-216763, cyclic-AMP response element-binding protein (CBP) using PRI-724 and ICG-001, the lymphoid enhanc-er binding factor (LEF)/T cell-specific transcription factor (TCF) system as well as Wnt inhibitory factor 1 (WIF1) and miR-17-5p using pinostilbene hydrate (PSH). Significant progress has been made in inhibiting Wnt and thus stop-ping the progression of liver fibrosis by diminishing key components for its action. Comprehending the role of the Wnt signaling pathway in liver fibrosis may lead to discov-ery of novel targets in liver fibrosis therapeutic strategies\' development.
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