1. Academic Validation
  2. Interleukin-1β augments the angiogenesis of endothelial progenitor cells in an NF-κB/CXCR7-dependent manner

Interleukin-1β augments the angiogenesis of endothelial progenitor cells in an NF-κB/CXCR7-dependent manner

  • J Cell Mol Med. 2020 May;24(10):5605-5614. doi: 10.1111/jcmm.15220.
Xia Fan 1 2 Luqing He 1 Qiaoxia Dai 1 Junhong He 1 Xiangjuan Chen 3 Xiaozhen Dai 4 Chi Zhang 1 5 Da Sun 6 Xue Meng 1 Shiyue Sun 1 Jiameng Huang 1 Jun Chen 1 7 Lin Lin 8 Liangmiao Chen 5 Yi Tan 1 Xiaoqing Yan 1
Affiliations

Affiliations

  • 1 Department of Pharmacy, Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, China.
  • 2 Department of Endocrinology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • 3 Department of Obstetrics and Gynecology, The first affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • 4 School of Biomedicine, Chengdu Medical College, Chengdu, China.
  • 5 Department of Endocrinology, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • 6 Institute of Life Sciences, Wenzhou University, Wenzhou, China.
  • 7 School of Nursing, Wenzhou Medical University, Wenzhou, China.
  • 8 Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Abstract

Endothelial progenitor cells (EPCs) are able to trigger angiogenesis, and pro-inflammatory cytokines have beneficial effects on angiogenesis under physiological and pathological conditions. C-X-C Chemokine Receptor type 7 (CXCR-7), receptor for stromal cell-derived factor-1, plays a critical role in enhancing EPC angiogenic function. Here, we examined whether CXCR7 mediates the pro-angiogenic effects of the inflammatory cytokine interleukin-1β (IL-1β) in EPCs. EPCs were isolated by density gradient centrifugation and angiogenic capability was evaluated in vitro by Matrigel capillary formation assay and fibrin gel bead assay. IL-1β elevated CXCR7 expression at both the transcriptional and translational levels in a dose- and time-dependent manner, and blockade of the nuclear translocation of NF-κB dramatically attenuated the IL-1β-mediated up-regulation of CXCR7 expression. IL-1β stimulation significantly promoted EPCs tube formation and this effect was largely impaired by CXCR7-siRNA transfection. IL-1β treatment stimulated extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, and inhibition of ERK1/2 phosphorylation partially impaired IL-1β-induced tube formation of EPCs but without significant effects on CXCR7 expression. Moreover, blocking NF-κB had no significant effects on IL-1β-stimulated ERK1/2 phosphorylation. These findings indicate that CXCR7 plays an important role in the IL-1β-enhanced angiogenic capability of EPCs and antagonizing CXCR7 is a potential strategy for inhibiting angiogenesis under inflammatory conditions.

Keywords

CXC chemokine receptor 7; angiogenesis; endothelial progenitor cells; extracellular signal-regulated kinase-1/2; interleukin-1β.

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