Abstract
Our preliminary data showed that VEGFR2 upregulation promoted renal ROS overproduction in high-fat diet- (HFD-) treated mice. Given that ROS-induced NLRP3 activation plays a central role in the pathogenesis of type 2 diabetic kidney injury, we evaluate whether VEGFR2 upregulation induces type 2 diabetic kidney injury via ROS-mediated NLRP3 activation and further explore the underlying mechanism. Our results showed that VEGFR2 knockdown decreased ROS overproduction, blocked NLRP3-dependent inflammation, and alleviated kidney damage in HFD-treated mice. Treatment with α-lipoic acid, a scavenger of ROS, lowered ROS overproduction and alleviated NLRP3-triggered kidney injury of HFD-treated mice. Collectively, the VEGFR2/ROS/NLRP3 signal is a critical therapeutic strategy for the kidney injury of HFD-treated mice. Purple sweet potato color (PSPC), a natural anthocyanin, can exert renal protection by inhibiting ROS in HFD-treated mice. Here, we provide a novel mechanism of PSPC against renal damage in HFD-treated mice by downregulating VEGFR2 expression.
Highlights
In recent years, type 2 diabetes mellitus (T2DM) has become more prevalent worldwide mainly due to excess calorie intake and low physical activity [1, 2]
Given our preliminary evidence showing that VEGFR2 stimulated ROS overproduction, the current study aims at investigating whether Purple sweet potato color (PSPC) alleviates kidney injury by downregulating VEGFR2-mediated oxidation stress and inflammation and further explaining the pathological mechanism underlying kidney damage in high-fat diet- (HFD-)treated mice
These results demonstrated that ROS overproduction was induced by VEGFR2 upregulation in the kidney of HFD-treated mice
Summary
Type 2 diabetes mellitus (T2DM) has become more prevalent worldwide mainly due to excess calorie intake and low physical activity [1, 2]. Further evidence shows that ROS-induced NLRP3 activation plays a key role in the pathological damage of DN [8]. Based on our previous finding that ROS-induced NLRP3 activation accelerated the kidney damage in HFD-treated mice, we hypothesize that VEGFR2 may be involved in the renal pathological injury via ROS-activated NLRP3 inflammatory signaling in HFD-treated mice. We confirm this hypothesis and Oxidative Medicine and Cellular Longevity explore the underlying mechanism of VEGFR2 mediating the renal injury in the HFD-treated mice
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