β-Amyrin ameliorates diabetic nephropathy in mice and regulates the miR-181b-5p/HMGB2 axis in high glucose-stimulated HK-2 cells.

Wenhua Xu, Hongwu Zhang, Qinfeng Zhang, Jialan Xu

Environmental toxicology 2022 Mar

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Diabetic nephropathy (DN) is a diabetic complication that can cause renal failure. β-amyrin has been identified to possess anti-diabetic property. This study was designed to evaluate the potential role of β-amyrin in DN and its underlying mechanism. Streptozotocin-induced diabetic mice were used as the in vivo model, and high glucose (HG)-stimulated human proximal tubular HK-2 cells were utilized as the in vitro model. Renal histological changes in mice were assessed by hematoxylin-eosin and periodic acid-Schiff staining. HK-2 cell viability and apoptosis were detected by Cell Counting Kit-8 assay and flow cytometry analysis, respectively. β-amyrin was found to ameliorate kidney injury in DN mice and suppressed inflammatory response as well as apoptosis of HG-stimulated HK-2 cells. miR-181-5p expression in murine renal tissues and HK-2 cells was detected by in situ hybridization (ISH) and fluorescence in situ hybridization (FISH). MiR-181b-5p, a previously identified target for diabetic kidney disease, was downregulated in renal tissues and HG stimulated HK-2 cells, and β-amyrin induced the upregulation of miR-181b-5p. Binding relationship between miR-181b-5p and high mobility group box 2 (HMGB2) was confirmed by luciferase reporter assay. MiR-181b-5p bound to 3' untranslated region of HMGB2 to suppress its expression. As shown by immunohistochemical staining and immunofluorescence staining, HMGB2 was upregulated in the in vivo and in vitro models of DN, and β-amyrin induced the downregulation of HMGB2. Moreover, HMGB2 overexpression neutralized the suppressive effects of miR-181b-5p elevation on the inflammatory response and apoptosis of HG-treated HK-2 cells. Overall, β-amyrin ameliorates DN in mice and suppresses inflammatory response and apoptosis of HG-stimulated HK-2 cells via the miR-181b-5p/HMGB2 axis. © 2021 Wiley Periodicals LLC.

Citation

Wenhua Xu, Hongwu Zhang, Qinfeng Zhang, Jialan Xu. β-Amyrin ameliorates diabetic nephropathy in mice and regulates the miR-181b-5p/HMGB2 axis in high glucose-stimulated HK-2 cells. Environmental toxicology. 2022 Mar;37(3):637-649