Mouse anti-Human NLRP2 monoclonal antibody, clone 2C21

Neuropilin 2 (NRP2) is a receptor for the vascular enclothelial growth factor (VEGF) and the sernaphorin (SEMA) families, 2 unrelated ligand families involved in angiogenesis and neuronal guidance. NRP2 specifically binds VEGF-A and VEGIF-C, although the biological relevance of these interactions in human endothelial cells is poorly understood. In this study, we show that both VEGF-A and VEGIF-C induce the interaction of NRP2 with VEGFR-2. This interaction correlated with an enhancement of the VEGIFIR-2 phosphorylation threshold. Overexpression of NRP2 in primary human enclothelial cells promoted cell survival induced by VEGF-A and VEGIF-C. In contrast, SEMA3F, another ligand for NRP2, was able to inhibit human enclothelial cell survival and migration induced by VEGIF-A and VEGF-C. Moreover, a siRINA targeting specifically NRP2 was a potent inhibitor of human enclothelial cell migration induced by VEGF-A and VEGIF-C. Thus, our data indicate that NlRP2 acts as a coreceptor that enhances human endothelial cell biological responses induced by VEGIF-A and VEGF-C.

Nonalcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation and inflammation in the liver, contributing to a broad spectrum of severe pathologies, such as metabolic syndrome and hepatocellular carcinoma. Presently, the pathogenesis that attributes to NAFLD has not been fully understood. NLRP2 has been shown to inhibit the NF-kappa B signaling, and thus may contribute to regulate the inflammatory response. However, its role in NAFLD is largely unclear. In the study, we found that NLRP2 was markedly decreased in liver tissues of individuals with severe steatosis, or in a genetic deficiency (ob/ob) mice. High fat diet (HFD) feeding also led to a significant reduction of NLRP2 in liver of mice. Then, the wild type (WT) and NLRP2 knockout (KO) mice were used to further explore the role of NLRP2 in the NAFLD progression. NLRP2 knockout mice exhibited severer metabolic syndrome and hepatic steatosis after HFD administration, as evidenced by the increased body weight, liver histological changes and lipid accumulation. Moreover, HFD feeding-induced inflammation was significantly accelerated by the loss of NLRP2, as evidenced by the increased expression of pro-inflammatory cytokines and activation of nuclear factor kappa B (NF-kappa B) pathway. In addition, oxidative stress triggered by HFD was further promoted by NLRP2 deletion through repressing NF-E2-related factor 2 (Nrf2) pathway. In vitro, we surprisingly found that promoting Nrf2 activation could attenuate NLRP2 knockout-accelerated inflammation and reactive oxygen species (ROS) generation. Therefore, our study indicated that NLRP2 might be a potential target for developing effective therapeutic strategy to prevent NAFLD progression. (C) 2018 Published by Elsevier Inc.