Cellular senescence pathway in cholangiocytes

The cellular senescence pathway in cholangiocytes refers to the process by which these biliary epithelial cells undergo permanent growth arrest in response to various insults, including oxidative stress, DNA damage, autophagy dysregulation, and repeated inflammatory injury. Senescent cholangiocytes develop a pro-inflammatory and pro-fibrotic secretory phenotype (SASP), promoting recruitment of immune cells, paracrine induction of senescence in neighboring cells, and fibrotic remodeling. This pathway is a major driver of pathologies in cholangiopathies, such as primary sclerosing cholangitis and primary biliary cholangitis, contributing to inflammation, ductular reaction, and liver fibrosis. The pathway includes prominent markers such as p16INK4a, p21, γH2AX, and SASP components. Recent therapeutic strategies in preclinical models are focused on inhibiting senescence induction (e.g., Ras inhibition), targeting components of the SASP, or employing senolytics to selectively eliminate senescent cholangiocytes

Other names

Cholangiocyte senescenceBiliary epithelial senescenceSenescence-associated secretory phenotype (SASP) in cholangiocytes

Inhibition of senescence induction (e.g., Ras pathway inhibitors) Clearance of senescent cells (senolytics)