title: Transcription factor E2-2 inhibits the proliferation of endothelial progenitor cells by suppressing autophagy.
abstract: Endothelial progenitor cells (EPCs) play a key role in repairing the injured vascular endothelium by differentiating into mature endothelial cells (ECs) or secreting cytokines in a paracrine manner to promote proliferation of existing ECs. However, the mechanisms underlying the proliferation of EPCs were not fully understood. In order to investigate the mechanisms of EPC proliferation, we isolated EPCs from mononuclear cells of mouse spleens. By manipulating E2-2 expression in vitro, we observed that E2-2 negatively regulated the proliferation of EPCs. Moreover, we noted that E2-2 negatively regulated the autophagy of EPCs by studying the expression of LC3II and p62. We also demonstrated that an autophagy inhibitor chloroquine (CQ) decreased the proliferation of EPCs in a concentration-dependent manner. Interestingly, CQ reversed the increase in cell proliferation and autophagy in the E2-2 knockdown group. Furthermore, we detected the expression of autophagy‑related protein ATG7 in EPCs which had been transfected with small interfering (siRNA)‑E2-2 and siRNA‑autophagy related 7 (ATG7) or were untransfected. Our study revealed that E2-2 regulated EPC autophagy via mediating ATG7 expression. We conclude that E2-2 inhibited EPC proliferation via suppressing their autophagy, and E2-2 regulated EPC autophagy by mediating the expression of ATG7.
authors.affiliation: Department of Postgraduate, Third Military Medical University, Chongqing 400038, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Institute of Cardiovascular Science of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Geriatrics, Kunming General Hospital of Chengdu Military Area, Kunming, Yunnan 650032, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Xia
authors.affiliation: Department of Geriatrics, Kunming General Hospital of Chengdu Military Area, Kunming, Yunnan 650032, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Cancer Institute of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
authors.forename: Xie-Wan
authors.initials: XW
authors.lastname: Chen
authors.affiliation: Department of Biochemistry, Third Military Medical University, Chongqing 400038, P.R. China.
authors.forename: Zhen-Hong
authors.initials: ZH
authors.lastname: Ni
authors.affiliation: Department of Geriatrics, Kunming General Hospital of Chengdu Military Area, Kunming, Yunnan 650032, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D001343:Autophagy; D000071193:Autophagy-Related Protein 7 / Q000235:genetics / Q000378:metabolism; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D066026:Endothelial Progenitor Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D000073940:Transcription Factor 4
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D034741:RNA, Small Interfering; C090743:Tcf4 protein, mouse; D000073940:Transcription Factor 4; D000071193:Autophagy-Related Protein 7