ADAM metallopeptidase domain 10 knockdown enables podocytes to resist high glucose stimulation by inhibiting pyroptosis via MAPK pathway

Sui,Chunjie; Zhou,Dan

doi:10.3892/etm.2023.11959

ADAM metallopeptidase domain 10 knockdown enables podocytes to resist high glucose stimulation by inhibiting pyroptosis via MAPK pathway

Authors:
- Chunjie Sui
- Dan Zhou
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Affiliations: Department of General Practice, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China, Department of Ophthalmology, The First Dongguan Affiliated Hospital of Guangdong Medical University, Dongguan, Guangdong 523710, P.R. China
Published online on: April 18, 2023 https://doi.org/10.3892/etm.2023.11959
Article Number: 260
Copyright: © Sui et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Diabetic nephropathy (DN) is a common severe microvascular complication of diabetes mellitus, and podocyte damage occurs in the early stages of DN. The urine of patients with various types of glomerular disease presents increased levels of ADAM metallopeptidase domain 10 (ADAM10). The present study aimed to explore the role of ADAM10 in podocyte damage. Therefore, the expression of ADAM10 in high glucose (HG)‑stimulated podocytes was measured by reverse transcription‑qPCR and western blot. Moreover, the effects of ADAM10 knockdown on podocyte inflammation and apoptosis were determined by ELISA, western blot and TUNEL assay after confirming the efficacy of cell transfection. Subsequently, the effects of ADAM10 knockdown on the MAPK pathway and pyroptosis were assessed by western blot. Through performing the aforementioned experiments, the role of the MAPK pathway in the regulatory effects of ADAM10 was then investigated by pretreating podocytes with pathway agonists. ADAM10 expression was upregulated in HG‑stimulated podocytes, while ADAM10 knockdown suppressed inflammation, apoptosis and pyroptosis of HG‑stimulated podocytes and inhibited the activation of the MAPK signaling pathway. However, when podocytes were pretreated with pathway agonists (LM22B‑10 or p79350), the aforementioned effects of ADAM10 knockdown were suppressed. The present study demonstrated that ADAM10 knockdown suppressed the inflammation, apoptosis and pyroptosis of HG‑stimulated podocytes by blocking the MAPK signaling pathway.

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