Tauroursodeoxycholic acid inhibits TGF‑β1‑induced renal fibrosis markers in cultured renal mesangial cells by regulating endoplasmic reticulum stress

Li,Li; Guo,Zhi-Yun; Wang,Juan; Fei,Pei-Pei; Ji,Yan-Fei; Xu,Cheng-Gang

doi:10.3892/etm.2022.11359

Tauroursodeoxycholic acid inhibits TGF‑β1‑induced renal fibrosis markers in cultured renal mesangial cells by regulating endoplasmic reticulum stress

Authors:
- Li Li
- Zhi-Yun Guo
- Juan Wang
- Pei-Pei Fei
- Yan-Fei Ji
- Cheng-Gang Xu
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Affiliations: Department of Nephrology, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai 201800, P.R. China
Published online on: May 9, 2022 https://doi.org/10.3892/etm.2022.11359
Article Number: 432
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Chronic kidney disease (CKD) has a worldwide prevalence of higher than 10% with an increasing mortality rate. As it involves the deterioration of renal function, it represents a serious risk to human health and, if left untreated, significantly lowers the quality of the patient's life. CKD is characterized by renal fibrosis. Studies have shown that transforming growth factor β1 (TGF‑β1), a key driving factor of renal fibrosis, is closely related to the activation of renal fibrosis pathways such as endoplasmic reticulum stress (ERS). Tauroursodeoxycholic acid (TUDCA), an endogenous bile acid derivative, can effectively inhibit endogenous ERS. Here, we explored the effects and actions of TUDCA on renal fibrosis by establishing a renal mesangial cell (RMC) model. The RMC was stimulated with TGF‑β1, and PCR and western blotting were used to detect the expression of ERS‑related chaperone proteins and fibrotic indicators. The expression of glucose‑regulated protein 78 (GRP78) was silenced in RMC cells to investigate the role of GRP78 in renal fibrosis. Finally, PCR and western blotting were used to detect the effects of TUDCA on the expression of GRP78, C/EBP homologous protein (CHOP), α‑smooth muscle actin (α‑SMA), and fibronectin (FN) in the TGF‑β1‑stimulated RMCs. The results showed that TUDCA significantly downregulated TGF‑β1‑induced levels of GRP78, CHOP, α‑SMA and FN in RMCs. In addition, downregulation of GRP78 inhibited the expression of FN and α‑SMA in the RMCs. In conclusion, downregulation of GRP78 and CHOP expression is one of the mechanisms by which TUDCA inhibits TGF‑β1‑induced renal mesangial cell fibrosis.

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