Summary
Published in eBioMedicine (2021), this peer-reviewed study used 3D Petri Dish® micro-molds to form scaffold-free 3D microtissues. Full citation: Xie, Guoxiang, et al. Conjugated secondary 12α-hydroxylated bile acids promote liver fibrogenesis
Conjugated secondary 12α-hydroxylated bile acids promote liver fibrogenesis
Research Overview
Serum and hepatic bile acid concentrations rise markedly in patients with liver fibrosis, but the roles of individual bile acid species in fibrogenesis were not fully understood. This study examined bile acid profiles in NASH patients and in several mouse fibrosis models, and probed mechanisms in cell lines, a 3D co-culture system, and an HSC-specific Tgr5 knockout mouse.
A group of conjugated 12α-hydroxylated bile acids — including taurodeoxycholate (TDCA) and glycodeoxycholate (GDCA) — was significantly elevated in NASH patients and in the mouse models. These bile acids increased hepatic stellate cell proliferation and fibrosis-marker expression, and administering TDCA and GDCA directly activated HSCs and promoted liver fibrogenesis.
Key Discoveries
- Conjugated 12α-OH bile acids (TDCA, GDCA) were elevated in NASH patients and fibrosis mouse models
- These bile acids increased HSC proliferation and fibrosis-related protein expression
- Mechanisms studied in cell lines, a 3D co-culture system, and an HSC-specific Tgr5 knockout mouse
