• Hao Zhou, Lin Gao, Zuo-Hua Yu, Shi-Jun Hong, Zhi-Wei Zhang, and Zhen-Zhen Qiu.
• Department of Urology, The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine (The People's Hospital of Fujian Province), Fuzhou, China.
• Nephrology (Carlton). 2019 Apr 1; 24 (4): 472-480.

AimTo understand the mechanism of long non-coding RNA (LncRNA) HOTAIR on renal interstitial fibrosis (RIF) by regulating Notch1 pathway via the modulation of miR-124.MethodsUnilateral ureteral occlusion (UUO) was used to construct the RIF rat model. HK-2 cells induced by TGF-β1 were used for the in vitro experiment, which were divided into five groups: Vehicle, TGF-β1, si-HOTAIR+TGF-β1, miR-124 inhibitor+TGF-β1, and si-HOTAIR+miR-124 inhibitor+TGF-β1 groups. Quantitative real-time PCR (qRT-PCR) and Western blot were performed to detect the expression of HOTAIR, miR-124, Notch1- and epithelial-to-mesenchymal transition (EMT)-related proteins.ResultsSignificant elevated HOTAIR and reduced miR-124 were presented in UUO rats and TGF-β1-induced HK-2 cells in a time-dependent manner, with the increased Jagged1 (JAG1), Notch1, NICD, α-SMA and FN, as well as the decreased E-cadherin (all P < 0.05). Compared with the TGF-β1 group, cells in the si-HOTAIR+TGF-β1 group were remarkably declined in cell proliferation and the protein expressions of JAG1, Notch1, NICD, α-SMA, and FN, but dramatically higher in E-cadherin expression (all P < 0.05). However, in comparison with the si-HOTAIR+TGF-β1 group, cells in the si-HOTAIR+miR-124 inhibitor+TGF-β1 group were apparently improved in proliferation and the protein expression of JAG1, Notch1, NICD, α-SMA, and FN, but substantially reduced in the level of E-cadherin protein (all P < 0.05).ConclusionSilencing lncRNA HOTAIR can up-regulate miR-124 to block Notch1 pathway, and thereby alleviating EMT and RIF, indicating HOTAIR as a potential target for RIF treatment.© 2018 Asian Pacific Society of Nephrology.

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