Tanshinone IIA Promoted Autophagy and Inhibited Inflammation to Alleviate Podocyte Injury in Diabetic Nephropathy

Abstract

Yuan Li,1 Tong Wu,1 Hongye Li,2 Mingming Liu,2 Haiyan Xu1 1School of Basic Medicine, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 2Lianyungang Clinical School of Xuzhou Medical University, Lianyungang, 222006, People’s Republic of ChinaCorrespondence: Haiyan Xu, School of Basic Medicine, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China, Email [email protected]: Tanshinone IIA (Tan-IIA) is widely used in patients with diabetic nephropathy (DN), but its protective effect on podocytes in DN has not been well studied. In this study, the effects of Tan-IIA on autophagy and inflammation of glomerular podocytes in DN were observed in vivo and in vitro, and the underlying mechanisms were investigated. Irbesartan, an angiotensin II receptor blocker, is a representative medication for the clinical treatment of DN. So irbesartan was chosen as a positive control drug.Methods: Eight-week-old male db/db mice were randomly divided into a DN group, an irbesartan group, and three groups receiving different doses of Tan-IIA. The control group consisted of the db/m littermate mice. Blood, urine, and kidney samples were taken from the mice after 12 weeks of continuous administration. Renal protection of Tan-IIA was evaluated using enzyme-linked immunosorbent assay kits, haematoxylin and eosin staining, transmission electron microscopy, Western blotting, and immunohistochemistry. In vitro, the protective effect of Tan-IIA on podocytes was explored using MPC5 cells cultured with high glucose.Results: Tan-IIA significantly improved renal pathological injury and relieved the renal dysfunction in DN. Compared with the DN group, Tan-IIA could up-regulate the expression of Synaptopodin, Podocin, LC3II/I and Beclin-1 (p < 0.05), and down-regulate the expression of p62, F4/80, NF-κB p65, IL-1β, TNF-α and IL-6 (p < 0.05) both in vivo and in vitro, suggesting that Tan-IIA treatment alleviated podocyte injury by promoting autophagy and inhibiting inflammation during DN. The levels of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR in Tan-IIA group were lower than those in DN group (p < 0.05), indicating that Tan-IIA inhibited the PI3K/Akt/mTOR signalling pathway in podocytes, which was a key pathway in regulating both autophagy and inflammation.Conclusion: Tan-IIA prevented podocyte injury in DN by fostering autophagy and inhibiting inflammation, at least in part via inhibition of the PI3K/Akt/mTOR signalling pathway.Keywords: tanshinone IIA, podocyte, diabetic nephropathy, autophagy, inflammation, PI3K/Akt/mTOR signalling pathway

Keywords

• tanshinone iia
• podocyte
• diabetic nephropathy
• autophagy
• inflammation
• pi3k/akt/mtor signalling pathway