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. 2024 Apr;196(4):1863-1875.
doi: 10.1007/s12010-023-04645-0. Epub 2023 Jul 13.

CircGAB1 Facilitates Podocyte Injury Through Sponging miR-346 and Activating MAPK6 in Diabetic Nephropathy

Pingyue Ma  1 , Yajing He  1 , Benyong Wang  1 , Donghao Qiu  1 , Qunhong Xu  2
Affiliations

CircGAB1 Facilitates Podocyte Injury Through Sponging miR-346 and Activating MAPK6 in Diabetic Nephropathy

Pingyue Ma et al. Appl Biochem Biotechnol. 2024 Apr.

Abstract

Background: Podocyte injury is very important process in diabetic nephropathy (DN) progression. Circular RNA (circRNA) takes part in regulating the advancement of DN. Herein, we explored the role and mechanism of circGAB1 in DN progression.

Methods: The abundances of circGAB1, microRNA-346 (miR-346) and mitogen-activated protein kinase 6 (MAPK6) were detected by qRT-PCR in DN serum samples and podocyte HGPC. Moreover, cell viability and apoptosis were determined using CCK8 assay and flow cytometry. Also, the protein levels of MAPK6, proliferation-related markers and apoptosis-related markers were analyzed by western blot. ELISA assay was used to measure the levels of inflammatory factors, and corresponding kits were used to detect the levels of oxidative stress-related markers. The relationship between miR-346 and circGAB1 or MAPK6 was distinguished by dual-luciferase reporter assay.

Results: CircGAB1 expression was increased in DN serum samples and HG-treated HGPC cells. CircGAB1 knockdown inhibited HG-induced apoptosis, inflammatory response and oxidative stress in HGPC cells. In terms of mechanism, circGAB1 sponged miR-346, and miR-346 targeted MAPK6. The inhibition effect of circGAB1 knockdown on HG-induced podocyte injury could be reversed by miR-346 inhibitor. Moreover, miR-346 overexpression repressed HG-induced podocyte injury by targeting MAPK6. CircGAB1 served as miR-346 sponge to positively regulate MAPK6.

Conclusion: CircGAB1 contributed to podocyte injury through mediating miR-346/MAPK6 axis, suggesting that circGAB1 might promote DN progression.

Keywords: CircGAB1; Diabetic nephropathy; MAPK6; Podocyte injury; miR-346.

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