Sex-Dependent Regulation of Liver Fibrosis in Primary Sclerosing Cholangitis: The Role of miR-125b, Androgen Receptors, TGF-β, and Apelin Signalling

This study explore how hormonal and molecular pathways contribute to the differential progression of liver fibrosis between men and women with PSC.

The study focuses on several key molecular players: miR-125b, androgen receptors, TGF-β signaling, and apelin signaling. Through experimental analysis, the authors demonstrate that these factors modulate the fibrotic response in a sex-dependent manner, with implications for how the disease progresses in different genders. miR-125b, a microRNA involved in regulating inflammatory responses, is shown to play a significant role in the fibrotic response, possibly by interacting with androgen receptors.

Androgen receptors are highlighted for their involvement in the progression of liver fibrosis, particularly in male patients. The androgen-driven signaling pathways may enhance fibrosis through interactions with other key players, such as TGF-β.

TGF-β (Transforming Growth Factor-beta), a critical regulator of fibrosis in many chronic liver diseases, is discussed as a central mediator of fibrosis in PSC, with differences in its expression and activity between sexes.

Apelin, an endogenous peptide involved in various physiological processes, is found to modulate fibrosis and liver inflammation in a sex-dependent manner, contributing to the complexity of PSC.

The study presents compelling evidence that sex hormones and their associated signaling pathways significantly influence the progression of liver fibrosis in PSC. The findings suggest that therapeutic approaches targeting these pathways, specifically tailored to male and female patients, could provide new avenues for managing PSC more effectively.