Calcitonin Gene-related Peptide Promotes Proliferation and Inhibits Apoptosis in Endothelial Progenitor Cells Via Inhibiting MAPK Signaling

Overview

Journal Proteome Sci

Publisher Biomed Central

Date 2018 Nov 27

PMID 30473635

Citations 9

Authors

Jianqun Wu

Song Liu

Zhao Wang

Shenghui Ma

Huan Meng

Jijie Hu

Affiliations

Soon will be listed here.

Abstract

Background: Calcitonin gene-related peptide (CGRP) contributes to bone formation by stimulating bone marrow stromal cell (BMSC) proliferation and differentiation. However, the proliferative and apoptotic effects of CGRP on bone marrow-derived endothelial progenitor cells (EPCs) have not been investigated.

Methods: We tested the effects of CGRP on EPC proliferation and apoptosis by Cell Counting Kit-8, flow cytometry, and studied the effects of CGRP on the expression of proliferation- and apoptosis-related markers in EPCs and the underlying mitogen-activated protein kinase (MAPK) signalling pathway by quantitative polymerase chain reaction and western blotting.

Results: We detected EPC markers (CD34, CD133 and VEGFR-2) in 7-day cultures and found that CGRP (10-10 M) promoted the proliferation of cultured EPCs, with a peak increase of 30% at 10 M CGRP. CGRP also upregulated the expression of proliferation-associated genes, including cyclin D1 and cyclin E, and increased the percentages of G2/M-phase and S-phase cells after incubation 72 h. CGRP inhibited serum deprivation (SD)-induced apoptosis in EPCs after 24 and 48 h and downregulated the expression of apoptosis-related genes, including caspase-3, caspase-8, caspase-9 and Bax. Phosphorylated (p-)ERK1/2, p-p38 and p-JNK protein levels in EPCs treated with CGRP were significantly lower than those in untreated EPCs. Pre-treatment with the calcitonin receptor-like receptor (CRLR) antagonist CGRP8-37 or a MAPK pathway inhibitor (PD98059, SB203580 or SP600125) completely or partially reversed the pro-proliferative and anti-apoptotic effects and the reduced p-ERK1/2, p-p38 and p-JNK expression induced by CGRP.

Conclusion: Our results show that CGRP exerts pro-proliferative and anti-apoptotic effects on EPCs and may act by inhibiting MAPK pathways.

Citing Articles

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