Anti-Apoptosis of Podocytes and Pro-Apoptosis of Mesangial Cells for Telmisartan in Alleviating Diabetic Kidney Injury

Xin Wei; Yabin Ma; Ya Li; Wenzhao Zhang; Yuting Zhong; Yue Yu; Li-Chao Zhang; Zhibin Wang; Ye Tu

doi:10.3389/fphar.2022.876469

Anti-Apoptosis of Podocytes and Pro-Apoptosis of Mesangial Cells for Telmisartan in Alleviating Diabetic Kidney Injury

Front Pharmacol. 2022 Apr 19:13:876469. doi: 10.3389/fphar.2022.876469. eCollection 2022.

Authors

Xin Wei¹, Yabin Ma², Ya Li³, Wenzhao Zhang⁴, Yuting Zhong⁵, Yue Yu⁶, Li-Chao Zhang⁵, Zhibin Wang⁴, Ye Tu²

Affiliations

¹ Department of Clinical Pharmacy, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
² Department of Pharmacy, Shanghai East Hospital, Tongji University, Shanghai, China.
³ Department of Clinical Pharmacy, Clinical Trial Center, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China.
⁴ Department of Critical Care Medicine, School of Anesthesiology, Naval Medical University, Shanghai, China.
⁵ Department of Pharmacy, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai, China.
⁶ Institute of Vascular Disease, Shanghai TCM-Integrated Hospital, Shanghai, China.

Abstract

Podocytes damage and mesangial cells expansion are two important pathological manifestations of glomerular injury in early diabetes. Telmisartan, as an angiotensin type 1 (AT₁) receptor inhibitor, could improve advanced glycation end (AGE) products or angiotensin Ⅱ (Ang Ⅱ)-induced podocytes injury including detachment or apoptosis. In this current paper, we first confirmed the protective effect of telmisartan on early diabetic kidney injury in type 1 diabetic rats. Telmisartan reduced the loss of podocin and inhibited the expression of α-SMA, reflecting its protective effect on podocyte injury and mesangial proliferation, respectively. More interestingly we observed an opposite effect of telmisartan on the cell viability and apoptosis of podocytes and mesangial cells in a high-glucose environment in vitro. The anti-apoptotic effect of telmisartan on podocytes might be related to its inhibition of swiprosin-1 (a protein can mediate high glucose-induced podocyte apoptosis) expression. While telmisartan induced a high expression of PPARγ in mesangial cells, and GW9662 (a PPARγ antagonist) partially inhibited telmisartan-induced apoptosis and reduced viability of mesangial cells. In addition, high glucose-induced PKCβ1/TGFβ1 expression in mesangial cells could be blocked by telmisartan. These data provide a more precise cellular mechanism for revealing the protective effect of telmisartan in diabetic kidney injury.

Keywords: apoptosis; diabetic kidney disease; mesangial cells; podocytes (MeSH: D050199); telmisartan (PubChem CID: 65.