Dataset Information

Purple Sweet Potato Color Attenuates Kidney Damage by Blocking VEGFR2/ROS/NLRP3 Signaling in High-Fat Diet-Treated Mice.

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 ?-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.

SUBMITTER: Zheng GH

PROVIDER: S-EPMC6360596 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Purple Sweet Potato Color Attenuates Kidney Damage by Blocking VEGFR2/ROS/NLRP3 Signaling in High-Fat Diet-Treated Mice.

Zheng Gui-Hong GH Shan Qun Q Mu Jing-Jing JJ Wang Yong-Jian YJ Zhang Zi-Feng ZF Fan Shao-Hua SH Hu Bin B Li Meng-Qiu MQ Xie Jun J Chen Ping P Wu Dong-Mei DM Lu Jun J Zheng Yuan-Lin YL

Oxidative medicine and cellular longevity 20190122

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 inflam ...[more]

PMID: 30805082

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Project description:Koumine (KM), one of the primary constituents of Gelsemium elegans, has been used for the treatment of inflammatory diseases such as rheumatoid arthritis, but whether KM impacts the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome remains unknown. This study aimed to explore the inhibitory effect of KM on NLRP3 inflammasome activation and the underlying mechanisms both in vitro using macrophages stimulated with LPS plus ATP, nigericin or monosodium urate (MSU) crystals and in vivo using an MSU-induced peritonitis model. We found that KM dose-dependently inhibited IL-1β secretion in macrophages after NLRP3 inflammasome activators stimulation. Furthermore, KM treatment efficiently attenuated the infiltration of neutrophils and suppressed IL-1β production in mice with MSU-induced peritonitis. These results indicated that KM inhibited NLRP3 inflammasome activation, and consistent with this finding, KM effectively inhibited caspase-1 activation, mature IL-1β secretion, NLRP3 formation and pro-IL-1β expression in LPS-primed macrophages treated with ATP, nigericin or MSU. The mechanistic study showed that, KM exerted a potent inhibitory effect on the NLRP3 priming step, which decreased the phosphorylation of IκBα and p65, the nuclear localization of p65, and the secretion of TNF-α and IL-6. Moreover, the assembly of NLRP3 was also interrupted by KM. KM blocked apoptosis-associated speck-like protein containing a CARD (ASC) speck formation and its oligomerization and hampered the NLRP3-ASC interaction. This suppression was attributed to the ability of KM to inhibit the production of reactive oxygen species (ROS). In support of this finding, the inhibitory effect of KM on ROS production was completely counteracted by H2O2, an ROS promoter. Our results provide the first indication that KM exerts an inhibitory effect on NLRP3 inflammasome activation associated with blocking the ROS/NF-κB/NLRP3 signal axis. KM might have potential clinical application in the treatment of NLRP3 inflammasome-related diseases.

Dataset Information

Purple Sweet Potato Color Attenuates Kidney Damage by Blocking VEGFR2/ROS/NLRP3 Signaling in High-Fat Diet-Treated Mice.

Publications

Purple Sweet Potato Color Attenuates Kidney Damage by Blocking VEGFR2/ROS/NLRP3 Signaling in High-Fat Diet-Treated Mice.

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