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Abstract: FR-PO204

Puerarin Attenuates Diabetic Nephropathy by Promoting Autophagy in Podocytes

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Li, Xueling, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
  • Zhu, Qingqing, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
  • Yan, Jiayi, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
  • Zhong, Yifei, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Background

Puerarin, an active compound of radix puerariae, is a major compound used in Chinese herbal medicines to treat patients with diabetic nephropathy (DN). In the previous studies, we showed that puerarin exerts renoprotective effects in a mouse model of streptozocin (STZ) induced diabetic nephropathy (DN) through activation of Sirt1 and anti-oxidative effects. Here, we further investigated the underlying mechanism mediating the renal protective effects of puerarin in DN.

Methods

We tested the effects of puerarin in STZ-induced diabetic mice and in cultured immortalized mouse podocytes treated with either normal (NG) or high glucose (HG). We performed western blot analysis, PCR analysis, immunohistochemistry to determine the molecular mechanisms mediated by puerarin in DN using both vivo and in vitro models. Immunoprecipitation combined with western blot analysis was used to determine acetylation of LKB1. shRNAs were used to knockdown HMOX1 and Sirt1 in cultured podocytes.

Results

We found that puerarin ameliorated STZ-induced kidney injury as shown by kidney histology. We also found that puerarin restored podocyte differential markers such as P-cadherin and ZO-1 in diabetic glomeruli. We also found that expression of HMOX-1 and Sirt1 was suppressed in diabetic glomeruli but restored by puerarin treatment as shown by both real-time PCR, western blot analysis, and immunostaining. In conditionally immortalized mouse podocytes, puerarin inhibited HG-induced apoptosis and restored the protein and mRNA levels of ZO-1, P-cadherin, HMOX-1, and Sirt1. Interestingly, we showed that puerarin decreased LKB1 acetylation, thereby promoting AMPK-dependent autophagy. Knockdown of HMOX-1 and Sirt1 expression or treatment with the autophagy inhibitor 3-MA abolished the protective effects of puerarin in HG-treated podocytes.

Conclusion

<span lang="EN-US" style="font-family:calibri,sans-serif; font-size:11pt; line-height:107%; margin:0px"><font color="#000000">Taken together, these results suggest that puerarin protects podocytes from diabetes-induced injury through HMOX1 and Sirt1-mediated upregulation of autophagy, a novel mechanism explaining its renal protective effects in DN. </font></span>

Funding

  • Government Support - Non-U.S.