Tohoku J. Exp. Med., 2023 May, 260(1)

Polysaccharide H-1-2 Ameliorates High Glucose-Induced Podocyte Dysfunction by Suppressing Epithelial-to-Mesenchymal Transition via Restoration of SIRT1 in Vivo and in Vitro

Minzhou Li,¹ Zhong Wu,¹ Wei Gao,¹ Kaiying Zhao,¹ Xiaobo Yang,¹ Huiyan Zhang,² Bin Deng² and Yang Niu²

¹Department of Traditional Chinese Medicine, the People's Hospital of Inner Mongolia Autonomous Region, Hohhot, Inner Mongolia, China
²College of Traditional Chinese Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China

Renal interstitial fibrosis, a pathological feature of diabetic nephropathy, is closely related to endothelial-to-mesenchymal transition (EMT). This study aimed to explore the effect of H-1-2, a polysaccharide of Pseudostellaria heterophylla, on high glucose (HG) induced-podocyte EMT in vivo and ex vivo. DBA/2 mice were given five consecutive days of streptozotocin injection to induce the diabetic nephropathy model. H-1-2 treatment effectively attenuated general states (bodyweight and blood glucose level) and reduced oral glucose tolerance, insulin tolerance, kidney index, as well as the level of serum urine nitrogen, serum creatinine, and urinary albumin excretion rate in diabetic nephropathy mice. The injury and EMT of podocytes in diabetic nephropathy mice were restrained by H-1-2. After exposing podocytes to HG, the impaired cell viability, apoptosis, the downregulation of nephrin, synaptopodin, sirtuin 1 (SIRT1) and P-cadherin, and the upregulation of N-cadherin were observed in podocytes. H-1-2 treatment could reverse these effects induced by HG. To uncover the mechanism underlying H-1-2 suppressing EMT, small interference RNA for SIRT1 was transfected into podocytes. Mechanically, silencing SIRT1 largely restrained the protective effect of H-1-2 on HG-induced podocytes. In conclusion, H-1-2 exerts a potential role in alleviating HG-induced dysfunction and EMT of podocytes in vivo and ex vivo via SIRT1.

Key words —— diabetic nephropathy; endothelial-to-mesenchymal transition; fibrosis; H-1-2; SIRT1

© 2023 Tohoku University Medical Press

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Tohoku J. Exp. Med 2023 May, 260(1), 35-45.

Correspondence: Minzhou Li, Department of Traditional Chinese Medicine, the People’s Hospital of Inner Mongolia Autonomous Region, No. 20 Zhaowuda Road, Saihan District, Hohhot, Inner Mongolia 010017, China.

e-mail: liminzhou521@163.com