title: Inhibitor of DNA-binding 1 promotes endothelial progenitor cell proliferation and migration by suppressing E2-2 through the helix-loop-helix domain.
abstract: Vascular endothelial damage is the major contributing factor to cardiovascular diseases. Recently, the therapeutic significance of endothelial progenitor cells (EPCs) has drawn increasing attention due to their roles in re-endothelialization following injury. The inhibitor of DNA-binding 1 (ID1) has been proven to promote EPC proliferation and migration, suggesting a critical function of ID1 in re-endothelialization. However, the underlying mechanisms remain undefined. In this study, ID1 was found to interact with E2-2 using immunoprecipitation analysis. Moreover, ID1 overexpression suppressed E2-2 expression and luciferase reporter activity; however, these effects were not observed in cells transfected with ID1 lacking the helix-loop-helix (HLH) domain (ID1ΔHLH). Further functional analysis corroborated that the upregulation of E2-2 markedly attenuated the ID1-mediated increase in EPC proliferation and migration. Furthermore, the HLH domain plays an important role in ID1-induced EPC proliferation and migration, as its deletion suppressed the positive regulatory effects of ID1 on EPC proliferation and migration. Taken together, the findings of our study confirm that ID1 promotes EPC proliferation and migration by suppressing E2-2 through the HLH domain in ID1. Therefore, ID1 may represent a potential therapeutic target for EPC-mediated re-endothelialization following vascular injury.
authors.affiliation: Cardiology Center of PLA, Xinqiao Hospital, The Third Military Medical University, Chongqing, Sichuan 400037, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Geriatrics, Kunming General Hospital of Chengdu Military Command, Kunming, Yunnan 650032, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Vascular Surgery, Kunming General Hospital of Chengdu Military Command, Kunming, Yunnan 650032, P.R. China.
authors.forename: Cunping
authors.initials: C
authors.lastname: Yin
authors.affiliation: Department of Geriatrics, Kunming General Hospital of Chengdu Military Command, Kunming, Yunnan 650032, P.R. China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Geriatrics, Kunming General Hospital of Chengdu Military Command, Kunming, Yunnan 650032, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Geriatrics, Kunming General Hospital of Chengdu Military Command, Kunming, Yunnan 650032, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Geriatrics, Kunming General Hospital of Chengdu Military Command, Kunming, Yunnan 650032, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D019556:COS Cells; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D066026:Endothelial Progenitor Cells / Q000378:metabolism*; D015870:Gene Expression; D018257:Helix-Loop-Helix Motifs / Q000235:genetics*; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology; D000073940:Transcription Factor 4
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051798:Inhibitor of Differentiation Protein 1; C090743:Tcf4 protein, mouse; D000073940:Transcription Factor 4