Activation of GPR120 by TUG891 ameliorated cisplatin-induced acute kidney injury via repressing ER stress and apoptosis - 19/04/20
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Graphical abstract |
Diagram of TUG891 in Cisplatin-induced AKI. TUG891 modulated the activities of PERK pathway of unfolded protein response, and consequently remitting apoptosis, ER stress and inflammation in cisplatin-induced AKI.
Highlights |
• | The GPR120 expression is downregulated in the kidneys of cisplatin-induced AKI. |
• | TUG891, a synthetic GPR120 agonist, protected against cisplatin-induced AKI. |
• | Activation of GPR120 by TUG891 inhibited ER stress and apoptosis in cisplatin injured kidneys. |
Abstract |
Activation of G protein-coupled receptor 120 (GPR120) could inhibit apoptosis and inflammation in cerebral ischemic injury and liver ischemia-reperfusion injury. However, whether GPR120 agonism exerted potential for cisplatin-induced acute kidney injury and the involved mechanisms remained unknown. In our study, pharmacological activation of GPR120 by TUG891 treatment remarkably reduced the elevated serum creatinine level and attenuated tubular injury. Cisplatin triggered ATF6, PERK and IRE1 pathways of unfolded protein response (UPR) of ER stress in the injured kidney tissue, as well as the downstream molecules eIF2α, ATF4 and XBP1. Protein of ER stress-mediated apoptosis, CHOP, was overexpressed in the cisplatin group. Oral application of TUG891 displayed effective inhibition of ER stress and apoptosis. TUG891 treatment significantly decreased the TUNEL positive cells and the flow cytometry of HK-2 cells delineated the similar results that the apoptosis rates were considerably reduced in the TUG891 group compared to cisplatin group. Collectively, activation of GPR120 by TUG891 exhibited renal protection against cisplatin-induced AKI via suppressing ER-associated apoptosis in tubular epithelial cells.
Le texte complet de cet article est disponible en PDF.Keywords : Cisplatin, Acute kidney injury, GPR120, Endoplasmic reticulum stress, Apoptosis
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Article 110056- juin 2020 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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