Quercetin attenuates the proliferation, inflammation, and oxidative stress of high glucose-induced human mesangial cells by regulating the miR-485-5p/YAP1 pathway

Abstract

Background Diabetic nephropathy (DN) is a kidney damage caused by diabetes and the main cause of end-stage renal disease. However, the current treatment of DN has many limitations. Quercetin is a bioflavonoid compound with therapeutic benefits in metabolic diseases. This study aims to determine the therapeutic potentials and underlying mechanism of quercetin on DN. Methods We collected blood samples from DN patients and healthy controls and treated human mesangial cells (HMCs) with high glucose (HG) to establish an in vitro model of DN. Then we assessed the expression difference of miR-485-5p as well as YAP1 in serum of DN patients and healthy controls and between HG-induced HMCs and control cells. qRT-PCR and western blot were performed to assess miR-485-5p and YAP1 expression levels; CCK-8 and ELISAs were used to examine cell proliferation, inflammation, and oxidative stress. Dual luciferase reporter assay was implemented to detect the binding of miR-485-5p and YAP1 mRNA sequence. Results Quercetin suppressed proliferation, inflammation, and oxidative stress of HMCs induced by HG. As for mechanism, miR-485-5p directly bound to YAP1 and inhibited YAP1 expression. The downregulation of miR-485-5p and upregulation of YAP1 were also observed in the serum of DN patients. Quercetin modulated miR-485-5p/YAP1 axis to regulate HG-induced inflammation and oxidative stress. Conclusion: Quercetin inhibits the proliferation, inflammation, and oxidative stress of HMCs induced by HG through miR-485-5p/YAP1 axis, which might provide a novel treatment strategy for DN.

Salviolone protects against high glucose‐induced proliferation, oxidative stress, inflammation, and fibrosis of human renal mesangial cells by upregulating membrane metalloendopeptidase expression

“…In our study, we found that the proliferation of HRMCs was promoted under HG condition, which was consistent with the results of previous studies (Wang et al, 2022; Zhu et al, 2021). Hyperglycemia‐induced oxidative stress has important roles in pathogenesis of diabetic nephropathy (Rosas‐Martínez et al, 2021; Vodosek Hojs et al, 2020), and HG could result in oxidative stress in renal mesangial cells (Wan et al, 2022; Wei et al, 2021). Similarly, our study showed that HG led to ROS production, MDA increase, and SOD activity reduction, suggesting that oxidative stress was induced by HG.…”

Molecular Mechanistic Pathways Targeted by Natural Compounds in the Prevention and Treatment of Diabetic Kidney Disease

“…Podocytes injury is one of the leading causes of proteinuria in patients with DKD, Liu et al found that quercetin can prevent glomerular damage in diabetic mice and repress podocyte apoptosis by inhibiting the EGFR signaling pathway [ 126 ]. A clinical study showed that the expression of miR-485-5p in peripheral blood of patients with DKD decreased significantly, through cell experiment, it was found that quercetin inhibited the expression of YAP1 by regulating the increase of miR-485-5p, thereby inhibiting HG-induced HMCs hyperproliferation, inflammation, and oxidative stress [ 127 ]. In addition, Du et al found that quercetin can also reduce the expression of yes-associated protein 1 (YAP1) by activating Hippo signaling pathway [ 128 ].…”

Quercetin Alleviates Lipopolysaccharide-Induced Inflammatory Response in Bovine Mammary Epithelial Cells by Suppressing TLR4/NF-κB Signaling Pathway

“…Quercetin is a flavonoid, which is a secondary metabolite of plant synthesis, and found in many fruits and vegetables ( 15 ). Quercetin has antioxidant and anti-inflammatory properties and modulates cell apoptosis, properties potentially of value in the treatment or prevention of mastitis ( 16 ). A previous research has shown that quercetin has an anti-cancer ability by inhibiting of growth of cells ( 17 ).…”