Turkish Journal of Gastroenterology
Basic & Translational - Original Article
Frizzled-2 small interfering RNA protects hepatic BRL-3A cells against Hypoxia / Reoxygenation via modulation of autophagy

Frizzled-2 small interfering RNA protects hepatic BRL-3A cells against Hypoxia / Reoxygenation via modulation of autophagy

1.

Department of Hepatobiliary Surgery II, State Key Laboratory of Organ Failure Research, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China

2.

Department of General Surgery, The Second Hospital of Shenzhen Baoan People’s Hospital Group, Shenzhen, China

Turk J Gastroenterol 2020; 31: 167-179
DOI: 10.5152/tjg.2020.18507
Read: 238 Downloads: 53 Published: 04 March 2020

Background/Aims: Autophagy plays a positive role in the prevention of liver damage after hepatic ischemia-reperfusion injury (HIRI); however, the molecular mechanism is still a mystery. Understanding the molecular events behind this injury may have important implications for devising proper strategies for managing liver injury. This study investigated the effects of Frizzled-2 expression on autophagy as well as Ca2+ concentration and apoptosis in BRL-3A cells.

Materials and Methods: BRL-3A cells exposed to the hypoxia/reoxygenation (H/R) condition were used as an in vitro HIRI hepatic cell model. The transfection of Frizzled-2 small interfering RNA (siRNA) or expression vector was performed to silence or overexpress Frizzled-2 in BRL-3A cells. The intracellular Ca2+ concentration was monitored by the fluorescence of Ca+. Western blot was used to detect autophagy-related proteins and apoptotic marker Caspase-3. The cellular autophagosome was observed by a transmission electron microscope.

Results: Beclin-1 and Atg7 expressions were considerably induced by H/R treatment, and this induction was attenuated by Frizzled-2 siRNA in BRL-3A cells. The LC3B-II/I ratio was inhibited by H/R treatment, although it was considerably induced by Frizzled-2 siRNA. The overexpression of Frizzled-2 induced intracellular Ca2+ concentration and expressed autophagy-related proteins and Caspase-3 except for the suppression of LC3B-II/I ratio in BRL-3A cells in the normoxia condition.

Conclusion: The overexpression of Frizzled-2 mimicked H/R treatment and suppressed autophagy activity, whereas Frizzled-2 siRNA induced cellular autophagy and attenuated the H/R-induced hepatic injury in BRL-3A cells. These developments suggest that Frizzled-2 siRNA protects hepatic BRL-3A cells from the injury of H/R via autophagy modulation.

Cite this article as: Hu X, Zhou C, He G, Cheng Y, Pan M, Gao Y. Frizzled-2 small interfering RNA protects hepatic BRL-3A cells against Hypoxia / Reoxygenation via modulation of autophagy. Turk J Gastroenterol 2020; 31(2): 167-79.

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