Treatment with quercetin inhibits SARS-CoV-2 N protein-induced acute kidney injury by blocking Smad3-dependent G1 cell-cycle arrest

• DOI: 10.1016/j.ymthe.2022.12.002
• Publication Date: 2022-12-12T16:51:44Z
• Authors: Wenjing Wu; Wenbiao Wang; Liying Liang; Junzhe Chen; Biao Wei; Xiao-Ru Huang; Xiaoqin Wang; Xueqing Yu; Hui-Yao Lan
• Keywords: 0303 health sciences; SARS-CoV-2; COVID-19; Mice, Inbred Strains; Cell Cycle Checkpoints; Acute Kidney Injury; Diabetes Mellitus, Experimental; 3. Good health; Mice; 03 medical and health sciences; Animals; Original Article; Quercetin

Increasing evidence shows that SARS-CoV-2 can infect kidneys and cause acute kidney injury (AKI) in critically ill COVID-19 patients. However, mechanisms through which induces AKI are largely unknown, treatment remains ineffective. Here, we report kidney-specific overexpressing N gene AKI, including tubular necrosis elevated levels of serum creatinine BUN 8-week-old diabetic db/db mice, become worse those with older age (16 weeks) underlying disease (DKD). Treatment quercetin, a purified product from traditional Chinese medicine (TCM) effective patients, significantly inhibit protein-induced mice or without DKD. Mechanistically, quercetin block the binding protein to Smad3, thereby inhibiting Smad3 signaling Smad3-mediated cell death via p16-dependent G1 cell-cycle arrest mechanism vivo vitro. In conclusion, is pathogenic severe particularly pre-existing DKD, Smad3-dependent mechanism. Importantly, identify may be an TCM compound capable by blocking N-Smad3-mediated pathway.