X Li1, H-M Yu. 1. Department of Thoracic Surgery, Zhejiang Putuo Hospital, Zhoushan, China. hrbliyisheng@163.com.
Abstract
OBJECTIVE: To clarify the role of HOXA-AS2 in the progression of diabetic nephropathy (DN) and the molecular mechanism. MATERIALS AND METHODS: Relative levels of HOXA-AS2 and microRNA-302b-3p (miRNA-302b-3p) in serum and kidney tissues of DN rats induced by STZ administration and controls were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Serum levels of interleukin-1β (IL-1β), Transforming Growth Factor-α (TNF-α), creatinine, and BUN, as well as blood glucose in DN rats administrated with vector or pcDNA-HOXA-AS2 lentivirus, were detected. Dual-Luciferase reporter gene assay was conducted to verify the interaction among HOXA-AS2, miRNA-302b-3p, and TIMP3. At last, the regulatory effects of HOXA-AS2/miRNA-302b-3p/TIMP3 axis on levels of IL-1β and TNF-α, proliferative, and apoptotic rates in podocytes undergoing high-level glucose treatment were explored. RESULTS: HOXA-AS2 was downregulated in STZ-induced DN rats. In vivo overexpression of HOXA-AS2 alleviated kidney injuries in DN rats, manifesting as elevations on serum levels of IL-1β, TNF-α, creatinine, BUN, and blood glucose. HOXA-AS2/miRNA-302b-3p/TIMP3 axis protected DN-induced inflammatory response, proliferation suppression, and apoptosis in podocytes following the high-glucose treatment. CONCLUSIONS: HOXA-AS2/miRNA-302b-3p/TIMP3 axis protects inflammatory response, proliferation suppression, and apoptosis in podocytes treated with high-level glucose, thus alleviating the deterioration of DN.
OBJECTIVE: To clarify the role of HOXA-AS2 in the progression of diabetic nephropathy (DN) and the molecular mechanism. MATERIALS AND METHODS: Relative levels of HOXA-AS2 and microRNA-302b-3p (miRNA-302b-3p) in serum and kidney tissues of DN rats induced by STZ administration and controls were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Serum levels of interleukin-1β (IL-1β), Transforming Growth Factor-α (TNF-α), creatinine, and BUN, as well as blood glucose in DN rats administrated with vector or pcDNA-HOXA-AS2 lentivirus, were detected. Dual-Luciferase reporter gene assay was conducted to verify the interaction among HOXA-AS2, miRNA-302b-3p, and TIMP3. At last, the regulatory effects of HOXA-AS2/miRNA-302b-3p/TIMP3 axis on levels of IL-1β and TNF-α, proliferative, and apoptotic rates in podocytes undergoing high-level glucose treatment were explored. RESULTS:HOXA-AS2 was downregulated in STZ-induced DN rats. In vivo overexpression of HOXA-AS2 alleviated kidney injuries in DN rats, manifesting as elevations on serum levels of IL-1β, TNF-α, creatinine, BUN, and blood glucose. HOXA-AS2/miRNA-302b-3p/TIMP3 axis protected DN-induced inflammatory response, proliferation suppression, and apoptosis in podocytes following the high-glucose treatment. CONCLUSIONS:HOXA-AS2/miRNA-302b-3p/TIMP3 axis protects inflammatory response, proliferation suppression, and apoptosis in podocytes treated with high-level glucose, thus alleviating the deterioration of DN.