Activation of autophagy through calcium-dependent AMPK/mTOR and PKC theta pathway causes activation of rat hepatic stellate cells under hypoxic stress

作者：Jin, Yuepeng; Bai, Yongyu; Ni, Haizhen; Qiang, Li; Ye, Lechi; Shan, Yunfeng; Zhou, Mengtao^*

来源：FEBS LETTERS, 2016, 590(5): 672-682.

DOI：10.1002/1873-3468.12090

• autophagy
• hepatic stellate cells
• hypoxic stress
• liver fibrosis

The activation of hepatic stellate cells (HSCs) is a prominent event in liver fibrogenesis. However, how HSCs are activated in the hypoxic microenvironment remains unclear. Here, we found that hypoxia increased autophagy in rat HSCs. Moreover, hypoxia induced an elevation of the intracellular calcium concentration ([Ca2+](i)), which was abolished by the cytosolic Ca2+ chelator or the phospholipase C (PLC)-specific inhibitor. Furthermore, hypoxia-induced autophagy involved the calcium-dependent activation of the 5'-adenosine monophosphate-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) and protein kinase C-theta (PKCh) pathways. In addition, hypoxia-mediated activation of HSCs depended on autophagy. Our results suggest that autophagy induction via the calcium-dependent AMPK-mTOR and PKCh pathways might lead to the activation of HSCs during hypoxic stress.

• 出版日期2016-3
• 单位温州医科大学