Premium
Effect of long non‐coding RNA growth arrest‐specific 5 on apoptosis in renal ischaemia/reperfusion injury
Author(s) -
Geng Xuemei,
Xu Xialian,
Fang Yi,
Zhao Shuan,
Hu Jiachang,
Xu Jiarui,
Jia Ping,
Ding Xiaoqiang,
Teng Jie
Publication year - 2019
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1111/nep.13476
Subject(s) - apoptosis , gas5 , transfection , small interfering rna , messenger rna , reperfusion injury , medicine , microbiology and biotechnology , rna , cancer research , ischemia , long non coding rna , biology , gene , biochemistry
Aim Long non‐coding RNA (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 ischaemia/reperfusion (I/R) injury. Apoptosis is an important pathogenesis during I/R injury. Here, we identified the effect of hypoxia‐responsive lncRNA growth arrest‐specific 5 (GAS5) on apoptosis in renal I/R injury. Methods Ischaemia/reperfusion injury in mice or hypoxia/re‐oxygenation (H/R) in human proximal renal tubular epithelial cells (HK‐2) was practiced to induce apoptosis. The kidneys and blood were collected at 24 h after reperfusion. The GAS5 messenger RNA (mRNA) expression and apoptosis‐related gene mRNA and protein levels, including p53, cellular inhibitor of apoptosis protein 2 (cIAP2) and thrombospondin‐1 (TSP‐1), were analysed. GAS5 small‐interfering RNA was transfected with H/R induced cells. Over‐expression of GAS5 was performed by plasmid transfection. Results Apoptotic cells significantly increased in I/R‐injured kidneys. GAS5 could be up‐regulated in kidneys at 24 h after reperfusion and 3 h after re‐oxygenation, combined with increased expression of its downstream apoptosis‐related proteins p53 and cIAP2. GAS5 small‐interfering RNA treatment down‐regulated the mRNA and protein levels of p53 and TSP‐1, and attenuated apoptosis induced by H/R in HK‐2 cells. Conversely, over‐expression of GAS5 up‐regulated the mRNA and protein levels of p53 and TSP‐1, and promoted apoptosis in HK‐2 cells. Conclusion Long non‐coding RNA 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.