Cell Biochem Funct. 2018 Jul;36(5):280-287. doi: 10.1002/cbf.3340. Epub 2018 Jun 25.

Mesenchymal stem cells enhance autophagy of human intrahepatic biliary epithelial cells in vitro.

Zhu Y^1,2, Wang Q¹, Tang X², Yao G², Sun L^1,2.

Abstract

Dysfunctional autophagy in intrahepatic biliary epithelial cells (IBECs) is the main mechanism underlying the pathogenesis of bile duct lesions in primary biliary cholangitis. Autophagy may be a key pathogenesis for aetiology of primary biliary cholangitis. Immunoblotting and immunofluorescence analyses were used for the evaluation of autophagy in human intrahepatic biliary epithelial cells (HiBECs) at various time points. Glycochenodeoxycholate (GCDC) induced autophagy in HiBECs; the ratio of microtubule-associated protein light chain 3-II/microtubule-associated protein light chain 3-I (LC3-II/LC3-I) expression markedly increased at 48 hours, and then declined. However, compared with cells treated with GCDC alone, the expression of LC3-II increased and the clearance of autophagosome enhanced in GCDC-treated cells cocultured with mesenchymal stem cells (MSCs). Furthermore, the level of phosphorylation of signal transducer and activator of transcription 3 (pSTAT3) decreased in HiBECs cocultured with MSCs relative to those cultured without MSCs. Following STAT3 silencing, decreased expression of phosphorylated eukaryotic initiation factor 2α was consistently observed. The present data suggest that mesenchymal stem cells may enhance autophagic flux of HiBECs through the inhibition of STAT3 activity.