Endoplasmic reticulum stress induces renal fibrosis in high‑fat diet mice via the TGF‑&beta;/SMAD pathway

Mu,Zhidan; Li,Bin; Chen,Mingyang; Liang,Chen; Gu,Wei; Su,Juan

doi:10.3892/mmr.2024.13360

Endoplasmic reticulum stress induces renal fibrosis in high‑fat diet mice via the TGF‑β/SMAD pathway

Authors:
- Zhidan Mu
- Bin Li
- Mingyang Chen
- Chen Liang
- Wei Gu
- Juan Su
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Affiliations: Department of Physiology and Pathophysiology, College of Basic Medicine, Dali University, Dali, Yunnan 671000, P.R. China, Department of Infection Disease, First Affiliated Hospital of Dali University, Dali, Yunnan 671000, P.R. China
Published online on: October 14, 2024 https://doi.org/10.3892/mmr.2024.13360
Article Number: 235
Copyright: © Mu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to investigate the role and mechanism of endoplasmic reticulum stress (ERS) in kidney injury caused by high‑fat diet (HFD). An obese mouse model was established via HFD feeding and intervention was performed by intraperitoneal injection of the ERS inhibitor salubrinal (Sal). Changes in the body and kidney weight and serum biochemical indices of the mice were determined. Hematoxylin and eosin and Masson staining were used to observe the pathological changes of renal tissues. Reverse transcription‑quantitative PCR and western blotting were used to observe the expression of ERS‑related proteins and TGF‑β/SMAD pathway‑related proteins. Immunohistochemistry was employed to explore the distribution of these proteins. Compared with those in the control group, the weight gain, lipid metabolism disorders and deterioration of renal function in the model group were greater. Malondialdehyde was elevated and superoxide dismutase was decreased in renal tissues. The mRNA and protein levels of TGF‑β1, SMAD2/3, α‑smooth muscle actin, collagen I, glucose‑regulated protein 78 and C/EBP‑homologous protein were markedly elevated, whereas SMAD7 was markedly decreased. Sal markedly inhibited the aforementioned effects. This investigation revealed a link between ERS and renal injury caused by HFD. ERS in HFD‑fed mice triggers renal fibrosis through the TGF‑β/SMAD pathway.

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