Piezo1: the Potential Novel Target for Radiation-induced Liver Fibrosis by Regulating FAP + fibroblasts.

Radiation-induced liver fibrosis is a serious complication of radiotherapy in patients with liver cancer and is characterized by excessive deposition of the extracellular matrix (ECM). The activation of cancer-associated fibroblasts (CAFs) is central to this event. Piezo1 is a mechanoreceptor that is highly expressed in liver tissue and is closely related to the fibrotic process. CAFs are highly heterogeneous, and different cell populations perform different functions. Recent studies have shown that fap, an important surface marker of the CAF membrane, presumably plays a "hub" role upstream of α-smooth muscle actin (α-SMA). This article reviews the unique microenvironment of liver cancer and liver fibrosis and the role of piezo1 and CAFs in liver fibrosis. Building upon the foundational evidence, we formulate a hypothesis that radiation-induced ECM remodeling activates Piezo1-mediated mechanotransduction, driving HIF-1α/TGF-β pathways to stimulate CAF activation (manifested by FAP upregulation), which may synergistically aggravate liver fibrosis and hepatocarcinogenesis.