AUTHOR=Dong Wenmin , Jia Chenglin , Li Ji , Zhou Yi , Luo Yun , Liu Jibo , Zhao Zhiguo , Zhang Jiaqi , Lin Shan , Chen Ying 

TITLE=Fisetin Attenuates Diabetic Nephropathy-Induced Podocyte Injury by Inhibiting NLRP3 Inflammasome

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.783706

DOI=10.3389/fphar.2022.783706

ISSN=1663-9812

ABSTRACT=<p>Diabetic nephropathy (DN) is one of the primary complications of diabetes. Fisetin is a flavonoid polyphenol that is present in several vegetables and fruits. The present study investigated the mechanisms of fisetin in DN-induced podocyte injury both <italic>in vitro</italic> and <italic>in vivo</italic>. The results revealed that fisetin ameliorated high glucose (HG)-induced podocyte injury and streptozotocin (STZ)-induced DN in mice. <italic>CDKN1B</italic> mRNA expression in the glomeruli of patients with DN decreased based on the Nephroseq dataset, and fisetin reversed <italic>CDKN1B</italic> expression at mRNA and protein levels in a dose-dependent manner in podocytes and mice kidney tissues. Furthermore, fisetin suppressed the phosphorylation of P70S6K, a downstream target of <italic>CDKN1B</italic>, activated autophagosome formation, and inhibited Nod-like receptor protein 3 (NLRP3) inflammasomes. Interfering <italic>CDKN1B</italic> reduced the protective effects of fisetin against high glucose-induced podocyte injury. Molecular docking results revealed a potential interaction between fisetin and <italic>CDKN1B</italic>. In summary, the present study revealed that fisetin alleviated high glucose-induced podocyte injury and STZ-induced DN in mice by restoring autophagy-mediated CDKN1B/P70S6K pathway and inhibiting NLRP3 inflammasome.</p>