5F peptide promotes endothelial differentiation of bone marrow stem cells through activation of ERK1/2 signaling

Synthetic apolipoprotein A-I (apoA-I) mimetic peptide 5F exhibits anti-atherosclerotic ability with largely unknown mechanism(s). Bone marrow (BM)-derived endothelial progenitor cells (EPCs) play a critical role in vascular integrity and function. The objective of the present study was to evaluate t...

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Veröffentlicht in:European journal of pharmacology 2020-06, Vol.876, p.173051-173051, Article 173051
Hauptverfasser: Zhang, Jia, Cui, Yuqi, Li, Xin, Xiao, Yuan, Liu, Lingjuan, Jia, Fengpeng, He, Jianfeng, Xie, Xiaoyun, Parthasarathy, Sampath, Hao, Hong, Fang, Ningyuan
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container_title European journal of pharmacology
container_volume 876
creator Zhang, Jia
Cui, Yuqi
Li, Xin
Xiao, Yuan
Liu, Lingjuan
Jia, Fengpeng
He, Jianfeng
Xie, Xiaoyun
Parthasarathy, Sampath
Hao, Hong
Fang, Ningyuan
description Synthetic apolipoprotein A-I (apoA-I) mimetic peptide 5F exhibits anti-atherosclerotic ability with largely unknown mechanism(s). Bone marrow (BM)-derived endothelial progenitor cells (EPCs) play a critical role in vascular integrity and function. The objective of the present study was to evaluate the effect of 5F on endothelial differentiation of BM stem cells and related mechanisms. Murine BM multipotent adult progenitor cells (MAPCs) were induced to differentiate into endothelial cells in vitro with or without 5F. The expression of endothelial markers vWF, Flk-1 and CD31 was significantly increased in the cells treated with 5F with enhanced in vitro vascular tube formation and LDL uptake without significant changes on proliferation and stem cell maker Oct-4 expression. Phosphorylated ERK1/2, not Akt, was significantly increased in 5F-treated cells. Treatment of MAPCs with PD98059 or small interfering RNA against ERK2 substantially attenuated ERK1/2 phosphorylation, and effectively prevented 5F-induced enhancement of endothelial differentiation of MAPCs. In vivo studies revealed that 5F increased EPCs number in the BM in mice after acute hindlimb ischemia that was effectively prevented with PD98059 treatment. These data supported the conclusion that 5F promoted endothelial differentiation of MAPCs through activation of ERK1/2 signaling.
doi_str_mv 10.1016/j.ejphar.2020.173051
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Bone marrow (BM)-derived endothelial progenitor cells (EPCs) play a critical role in vascular integrity and function. The objective of the present study was to evaluate the effect of 5F on endothelial differentiation of BM stem cells and related mechanisms. Murine BM multipotent adult progenitor cells (MAPCs) were induced to differentiate into endothelial cells in vitro with or without 5F. The expression of endothelial markers vWF, Flk-1 and CD31 was significantly increased in the cells treated with 5F with enhanced in vitro vascular tube formation and LDL uptake without significant changes on proliferation and stem cell maker Oct-4 expression. Phosphorylated ERK1/2, not Akt, was significantly increased in 5F-treated cells. Treatment of MAPCs with PD98059 or small interfering RNA against ERK2 substantially attenuated ERK1/2 phosphorylation, and effectively prevented 5F-induced enhancement of endothelial differentiation of MAPCs. In vivo studies revealed that 5F increased EPCs number in the BM in mice after acute hindlimb ischemia that was effectively prevented with PD98059 treatment. 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Bone marrow (BM)-derived endothelial progenitor cells (EPCs) play a critical role in vascular integrity and function. The objective of the present study was to evaluate the effect of 5F on endothelial differentiation of BM stem cells and related mechanisms. Murine BM multipotent adult progenitor cells (MAPCs) were induced to differentiate into endothelial cells in vitro with or without 5F. The expression of endothelial markers vWF, Flk-1 and CD31 was significantly increased in the cells treated with 5F with enhanced in vitro vascular tube formation and LDL uptake without significant changes on proliferation and stem cell maker Oct-4 expression. Phosphorylated ERK1/2, not Akt, was significantly increased in 5F-treated cells. Treatment of MAPCs with PD98059 or small interfering RNA against ERK2 substantially attenuated ERK1/2 phosphorylation, and effectively prevented 5F-induced enhancement of endothelial differentiation of MAPCs. In vivo studies revealed that 5F increased EPCs number in the BM in mice after acute hindlimb ischemia that was effectively prevented with PD98059 treatment. These data supported the conclusion that 5F promoted endothelial differentiation of MAPCs through activation of ERK1/2 signaling.</description><subject>Animals</subject><subject>Apolipoprotein A-I mimetic peptide</subject><subject>Bone marrow stem cell</subject><subject>Bone Marrow Transplantation</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Endothelial differentiation</subject><subject>Endothelial progenitor cell</subject><subject>Endothelial Progenitor Cells - cytology</subject><subject>Endothelial Progenitor Cells - drug effects</subject><subject>Endothelial Progenitor Cells - metabolism</subject><subject>Endothelium, Vascular - cytology</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - metabolism</subject><subject>ERK1/2</subject><subject>Intercellular Signaling Peptides and Proteins - pharmacology</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Mesenchymal Stem Cells - cytology</subject><subject>Mesenchymal Stem Cells - drug effects</subject><subject>Mesenchymal Stem Cells - metabolism</subject><subject>Mice, Inbred C57BL</subject><subject>Mitogen-Activated Protein Kinase 1 - genetics</subject><subject>Octamer Transcription Factor-3 - genetics</subject><subject>Rats</subject><subject>RNA, Small Interfering - genetics</subject><subject>Transfection</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtKxDAUhoMoOo6-gUiWbjrm2stGEHFUHBDEfUjTk5kMbVOTjOLb26Hq0tWBw3cu_4fQBSULSmh-vV3AdtjosGCEja2CE0kP0IyWRZWRgrJDNCOEioxVVXWCTmPcEkJkxeQxOuGMCsmZnKFBLvEAQ3IN4CH4zieIGPrGpw20Tre4cdZCgD45nZzvsbe49j3gTofgP3FM0GEDbRtx2gS_W2-wNsl9_MH3r8_0muHo1r1uXb8-Q0dWtxHOf-ocvS3v3-4es9XLw9Pd7SozPGcpk0TktrC8pFyyhlipc1E0lJq6rCnllWZlZWjJDSc1gNaS1JUwRWm5qOtRxhxdTWvHUO87iEl1Lu7_1D34XVSMF4KLvCjzERUTaoKPMYBVQ3BjvC9FidqrVls1qVZ71WpSPY5d_lzY1R00f0O_bkfgZgJgjPnhIKhoHPQGGhfAJNV49_-Fb1imkcM</recordid><startdate>20200605</startdate><enddate>20200605</enddate><creator>Zhang, Jia</creator><creator>Cui, Yuqi</creator><creator>Li, Xin</creator><creator>Xiao, Yuan</creator><creator>Liu, Lingjuan</creator><creator>Jia, Fengpeng</creator><creator>He, Jianfeng</creator><creator>Xie, Xiaoyun</creator><creator>Parthasarathy, Sampath</creator><creator>Hao, Hong</creator><creator>Fang, Ningyuan</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20200605</creationdate><title>5F peptide promotes endothelial differentiation of bone marrow stem cells through activation of ERK1/2 signaling</title><author>Zhang, Jia ; Cui, Yuqi ; Li, Xin ; Xiao, Yuan ; Liu, Lingjuan ; Jia, Fengpeng ; He, Jianfeng ; Xie, Xiaoyun ; Parthasarathy, Sampath ; Hao, Hong ; Fang, Ningyuan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-5046f7f381352d0f5a647d11cb8b1139a289c183c30beeaa50b94c78f34bb173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Apolipoprotein A-I mimetic peptide</topic><topic>Bone marrow stem cell</topic><topic>Bone Marrow Transplantation</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Proliferation - drug effects</topic><topic>Endothelial differentiation</topic><topic>Endothelial progenitor cell</topic><topic>Endothelial Progenitor Cells - cytology</topic><topic>Endothelial Progenitor Cells - drug effects</topic><topic>Endothelial Progenitor Cells - metabolism</topic><topic>Endothelium, Vascular - cytology</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Endothelium, Vascular - metabolism</topic><topic>ERK1/2</topic><topic>Intercellular Signaling Peptides and Proteins - pharmacology</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Mesenchymal Stem Cells - cytology</topic><topic>Mesenchymal Stem Cells - drug effects</topic><topic>Mesenchymal Stem Cells - metabolism</topic><topic>Mice, Inbred C57BL</topic><topic>Mitogen-Activated Protein Kinase 1 - genetics</topic><topic>Octamer Transcription Factor-3 - genetics</topic><topic>Rats</topic><topic>RNA, Small Interfering - genetics</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Jia</creatorcontrib><creatorcontrib>Cui, Yuqi</creatorcontrib><creatorcontrib>Li, Xin</creatorcontrib><creatorcontrib>Xiao, Yuan</creatorcontrib><creatorcontrib>Liu, Lingjuan</creatorcontrib><creatorcontrib>Jia, Fengpeng</creatorcontrib><creatorcontrib>He, Jianfeng</creatorcontrib><creatorcontrib>Xie, Xiaoyun</creatorcontrib><creatorcontrib>Parthasarathy, Sampath</creatorcontrib><creatorcontrib>Hao, Hong</creatorcontrib><creatorcontrib>Fang, Ningyuan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Jia</au><au>Cui, Yuqi</au><au>Li, Xin</au><au>Xiao, Yuan</au><au>Liu, Lingjuan</au><au>Jia, Fengpeng</au><au>He, Jianfeng</au><au>Xie, Xiaoyun</au><au>Parthasarathy, Sampath</au><au>Hao, Hong</au><au>Fang, Ningyuan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>5F peptide promotes endothelial differentiation of bone marrow stem cells through activation of ERK1/2 signaling</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2020-06-05</date><risdate>2020</risdate><volume>876</volume><spage>173051</spage><epage>173051</epage><pages>173051-173051</pages><artnum>173051</artnum><issn>0014-2999</issn><eissn>1879-0712</eissn><abstract>Synthetic apolipoprotein A-I (apoA-I) mimetic peptide 5F exhibits anti-atherosclerotic ability with largely unknown mechanism(s). Bone marrow (BM)-derived endothelial progenitor cells (EPCs) play a critical role in vascular integrity and function. The objective of the present study was to evaluate the effect of 5F on endothelial differentiation of BM stem cells and related mechanisms. Murine BM multipotent adult progenitor cells (MAPCs) were induced to differentiate into endothelial cells in vitro with or without 5F. The expression of endothelial markers vWF, Flk-1 and CD31 was significantly increased in the cells treated with 5F with enhanced in vitro vascular tube formation and LDL uptake without significant changes on proliferation and stem cell maker Oct-4 expression. Phosphorylated ERK1/2, not Akt, was significantly increased in 5F-treated cells. Treatment of MAPCs with PD98059 or small interfering RNA against ERK2 substantially attenuated ERK1/2 phosphorylation, and effectively prevented 5F-induced enhancement of endothelial differentiation of MAPCs. In vivo studies revealed that 5F increased EPCs number in the BM in mice after acute hindlimb ischemia that was effectively prevented with PD98059 treatment. These data supported the conclusion that 5F promoted endothelial differentiation of MAPCs through activation of ERK1/2 signaling.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>32145325</pmid><doi>10.1016/j.ejphar.2020.173051</doi><tpages>1</tpages></addata></record>
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subjects Animals
Apolipoprotein A-I mimetic peptide
Bone marrow stem cell
Bone Marrow Transplantation
Cell Differentiation - drug effects
Cell Proliferation - drug effects
Endothelial differentiation
Endothelial progenitor cell
Endothelial Progenitor Cells - cytology
Endothelial Progenitor Cells - drug effects
Endothelial Progenitor Cells - metabolism
Endothelium, Vascular - cytology
Endothelium, Vascular - drug effects
Endothelium, Vascular - metabolism
ERK1/2
Intercellular Signaling Peptides and Proteins - pharmacology
MAP Kinase Signaling System - drug effects
Mesenchymal Stem Cells - cytology
Mesenchymal Stem Cells - drug effects
Mesenchymal Stem Cells - metabolism
Mice, Inbred C57BL
Mitogen-Activated Protein Kinase 1 - genetics
Octamer Transcription Factor-3 - genetics
Rats
RNA, Small Interfering - genetics
Transfection
title 5F peptide promotes endothelial differentiation of bone marrow stem cells through activation of ERK1/2 signaling
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