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

Abstract

Background: Diabetic nephropathy constitutes a large proportion of end-stage kidney failure in diabetic patients. However, the underlying molecular mechanisms remain unclear. Methods: 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. Results: 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. Conclusion: CASC2 could alleviate the degree and process of apoptosis, inflammation, and fibrosis in diabetic nephropathic models by regulating the miR-144/SOCS2 axis.

Journal

Journal ID (publisher-id): KBR

Journal ID (nlm-ta): Kidney Blood Press Res

Journal ID (doi): 10.1159/issn.1420-4096

Title: Kidney and Blood Pressure Research

Publisher: S. Karger AG

ISSN (Print): 1420-4096

ISSN (Electronic): 1423-0143

Publication date Subscription-year: 2020

Publication date (Print): December 2020

Publication date (Electronic): 23 November 2020

Volume: 45

Issue: 6

Pages: 837-849

Affiliations

_aThe First Affiliated Hospital of Soochow University, Suzhou, China

_bDepartment of Nephrology, People’s Hospital of XueCheng, Zaozhuang, China

Author notes

*Yan Xie, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006 (China), [e-mail]

Article

Publisher ID: 508078 Other ID: Kidney Blood Press Res 2020;45:837–849

DOI: 10.1159/000508078

PubMed ID: 33227790

Copyright statement: © 2020 The Author(s). Published by S. Karger AG, Basel

License:

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Page count

Figures: 6, Tables: 1, Pages: 13

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Categories

Subject: Research Article