LncRNA H19 as a key regulator in biliary atresia: insights into pathogenesis and potential therapeutic targets

Biliary atresia (BA) is a devastating cholangiopathy, characterized by onset of persistent cholestatic jaundice during the neonatal period. The etiology of BA remains incompletely understood and is considered multifactorial. Recent evidence has identified that the long non-coding RNA H19 (H19) is among the critical regulators involved in this pathological process. This review summarizes the current understanding of the H19 in the pathogenesis of BA.

The pathogenesis of BA is considered to be closely associated with impaired biliary epithelial barrier function. This barrier defect renders cholangiocytes more susceptible to injury and promotes bile acid retention. Within this pathological microenvironment, multiple factors such as bile acids and estrogen significantly upregulate H19 expression, with its level showing a positive correlation with the severity of BA. Up-regulated H19 is predominantly enriched in cholangiocytes and can be delivered to adjacent hepatocytes, hepatic stellate cells, macrophages, and liver sinusoidal endothelial cells, where it orchestrates cellular activities via diverse signaling pathways. By integrating and amplifying injury signals, H19 ultimately exacerbates inflammatory responses and fibrotic processes, driving the development and progression of BA. Additionally, emerging evidence suggests that certain traditional Chinese medicines exert anti-fibrotic effects by targeting H19, further highlighting its potential as a therapeutic target.

This review comprehensively and systematically delineates the key regulatory network of H19 in BA, highlighting its translational potential as a novel therapeutic target and laying a theoretical foundation for future mechanistic exploration and clinical translation.