Inhibition of miR-34a-5p alleviates hypoxia-reoxygenation injury by enhancing autophagy in steatotic hepatocytes

Chuanjiang Li; Kai Wang; Linghong Guo; Hang Sun; Hai Huang; XinXin Lin; Qingping Li

doi:10.1242/bio.033290

Inhibition of miR-34a-5p alleviates hypoxia-reoxygenation injury by enhancing autophagy in steatotic hepatocytes

Biol Open. 2018 Mar 26;7(3):bio033290. doi: 10.1242/bio.033290.

Authors

Chuanjiang Li^{1

2}, Kai Wang³, Linghong Guo³, Hang Sun³, Hai Huang⁴, XinXin Lin⁵, Qingping Li³

Affiliations

¹ Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China licj@smu.edu.cn.
² Department of Surgery, Linzhi Municipal People's Hospital, Linzhi, Tibet 860100, China.
³ Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
⁴ Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA.
⁵ The First Clinical College, Southern Medical University, Guangzhou, Guangdong 510515, China.

Abstract

Hypoxia-reoxygenation (H/R) injury in steatotic hepatocytes has been implicated in liver dysfunction after liver transplantation. MicroRNAs (miRs) play important roles in regulating several cell biology mechanisms related to H/R injury. However, the role of miRs in regulating H/R injury in steatotic hepatocytes is still unclear. We established an in vitro model for studying H/R injury in steatotic hepatocytes and identified miR-34a-5p as a miR that was substantially upregulated in steatotic hepatocytes under H/R challenge. MiR-34a-5p expression was modified by transfecting miR-34a-5p mimic and inhibitor into H/R-challenged steatotic hepatocytes. We found that inhibition of miR-34a-5p alleviated H/R-induced apoptosis and promoted post-H/R proliferation in steatotic hepatocytes. Whereas, overexpression of miR-34a-5p augmented H/R-induced apoptosis and prohibited post-H/R proliferation. By examining autophagy, our data demonstrated that miR-34a-5p suppressed autophagy in H/R-challenged steatotic hepatocytes, induction of autophagy partially rescued the exaggeration of H/R injury induced by miR-34a-5p mimic, while inhibition of autophagy impaired the protection of the miR-34a-5p inhibitor against H/R injury. In conclusion, miR-34a-5p is crucial in exaggerating H/R injury, likely by suppressing autophagy in steatotic hepatocytes. Inhibition of miR-34a may be a promising strategy to protect steatotic hepatocytes against H/R-injury.

Keywords: Autophagy; Hypoxia/Reoxygenation injury; MiR-34a-5p; Steatosis.