The effect of long noncoding RNA GAS5 on apoptosis in renal ischemia/reperfusion injury.

AIM: long noncoding RNAs (lncRNAs) have been shown to play a critical role in a variety of pathophysiological processes, such as cell proliferation, apoptosis and migration. However, there were few studies addressing the function of lncRNAs in renal ischemia/reperfusion (I/R) injury. Apoptosis is an important pathogenesis during I/R injury. Here we identified the effect of hypoxia-responsive lncRNA GAS5 on apoptosis in renal I/R injury.

METHODS: I/R injury in mice or hypoxia/reoxygenation (H/R) in renal tubular epithelial cells (HK-2 cells) was practiced to induce apoptosis. The kidneys and blood were collected at 24h after reperfusion. The GAS5 mRNA expression and apoptosis-related gene mRNA and protein levels including p53, cIAP2 and TSP-1 were analyzed. GAS5 siRNA was transfected with H/R induced cells. Overexpression of GAS5 was performed by plasmid transfection.

RESULTS: Apoptotic cells significantly increased in I/R injuried kidneys. GAS5 could be upregulated in kidneys at 24h after reperfusion and 3h after reoxygenation, combined with increased expression of its downstream apoptosis-related proteins p53 and cIAP2. GAS5 siRNA treatment downregulated the mRNA and protein levels of p53 and TSP-1, and attenuated apoptosis induced by H/R in HK-2 cells. Conversely, overexpression of GAS5 upregulated the mRNA and protein levels of p53 and TSP-1, and promoted apoptosis in HK-2 cells.

CONCLUSION: lncRNA GAS5 induced by I/R injury could promote apoptosis in kidney. TSP-1 might be one of the downstream effectors of GAS5, which will be explored in the future. This article is protected by copyright. All rights reserved.