AUTHOR=Sheng Hongqin , Zhang Duo , Zhang Jiaqi , Zhang Yanmei , Lu Zhaoyu , Mao Wei , Liu Xusheng , Zhang Lei TITLE=Kaempferol attenuated diabetic nephropathy by reducing apoptosis and promoting autophagy through AMPK/mTOR pathways JOURNAL=Frontiers in Medicine VOLUME=9 YEAR=2022 URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.986825 DOI=10.3389/fmed.2022.986825 ISSN=2296-858X ABSTRACT=Introduction

Renal podocyte injury, apoptosis and autophagy are involved in the occurrence and development of diabetic nephropathy (DN). Kaempferol (KPF) has the promotion of autophagy and inhibition of apoptosis properties in the development of miscellaneous diseases, but these functions in DN have not yet been elucidated.

Methods

We used db/db mice to evaluate the protective role of KPF on DN. The anti-DN effect of KPF was evaluated by urine albumin-to-creatinine ratio and pathological changes of kidney tissue. Injury of podocytes was observed through Transmission electron microscopy. Immunofluorescence, Western blot, and Immunohistochemistry were used to detect the protein expression of podocyte-associated molecules, autophagy, and AMPK/mTOR pathway.

Results

We demonstrated that KPF treatment significantly attenuated diabetes-induced albuminuria and glycolipid metabolism dysfunction. In addition, KPF alleviated mesangial matrix expansion, glomerular basement membrane thickening and loss or fusion of podocytes. Mechanistically, KPF treatment regulated the expression of autophagic proteins (upregulated LC3II, Beclin-1, Atg7 and Atg 5, and downregulated p62/SQSTM1), accompanied by inhibited renal apoptosis (downregulated Caspase 3 and Bax, and upregulated Bcl-2). KPF could significantly regulate the AMPK/mTOR signaling pathways by increasing p-AMPK and decreasing p-mTOR expressions.

Discussion

In conclusion, KPF might have a protective effect on DN through reduced apoptosis and enhanced podocytes autophagy, which were correlated with regulating AMPK/mTOR pathways.