LncRNA CASC2 Alleviates the Progression of Diabetic Nephropathy by Regulating the miR-144/SOCS2 Signalling Axis.

Xiao-Qiang Min, Yan Xie

Kidney & blood pressure research 2020

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Diabetic nephropathy constitutes a large proportion of end-stage kidney failure in diabetic patients. However, the underlying molecular mechanisms remain unclear. Db/db diabetic mouse models and high glucose (HG)-induced human renal mesangial cells (HRMCs) were used as research models in vivo and in vitro. The expression of cancer susceptibility candidate 2 (CASC2) was quantified by qRT-PCR. The regulatory role of CASC2 in cell apoptosis, inflammatory factor release, and fibrosis was verified by flow cytometry, qRT-PCR, and Western blot assay, respectively. The bioinformatics prediction software DIANA and starBase v2.0 were used to predict the putative binding sites. The interactions among CASC2, miR-144, and SOCS2 were explored by the luciferase assay and Western bolt assay. The expression of CASC2 in diabetic mouse models and HG-induced HRMCs was lower than that in the control (p < 0.05). Overexpression of CASC2 resulted in a decrease in the apoptosis rate, inflammatory factor release (TNF-α, IL-6, and IL-1β), expression of cleaved caspase-3, and fibrotic proteins (fibronectin, Col-IV, and TGF-β1) and an increase in Bcl-2 expression. Inhibition of CASC2 caused increased expression of miR-144. Furthermore, mechanistic investigations confirmed that activation of the miR-144/SOCS2 regulatory loop by overexpression of miR-144 reversed the in vitro effects of CASC2 on inhibiting cell apoptosis, inflammatory factor release, and fibrosis. In addition, simultaneous overexpression of miR-144 and SOCS2 further increased the inhibition of cell apoptosis, inflammatory factor release, and fibrosis by CASC2. CASC2 could alleviate the degree and process of apoptosis, inflammation, and fibrosis in diabetic nephropathic models by regulating the miR-144/SOCS2 axis. © 2020 The Author(s). Published by S. Karger AG, Basel.

Citation

Xiao-Qiang Min, Yan Xie. LncRNA CASC2 Alleviates the Progression of Diabetic Nephropathy by Regulating the miR-144/SOCS2 Signalling Axis. Kidney & blood pressure research. 2020;45(6):837-849