Inhibitor of DNA-binding 1 promotes endothelial progenitor cell proliferation and migration by suppressing E2-2 through the helix-loop-helix domain

Yu,Yang; Liang,Yuan; Yin,Cunping; Liu,Xiaoli; Su,Yong; Zhang,Li; Wang,Hong

doi:10.3892/ijmm.2016.2734

Inhibitor of DNA-binding 1 promotes endothelial progenitor cell proliferation and migration by suppressing E2-2 through the helix-loop-helix domain

Authors:
- Yang Yu
- Yuan Liang
- Cunping Yin
- Xiaoli Liu
- Yong Su
- Li Zhang
- Hong Wang
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Affiliations: Cardiology Center of PLA, Xinqiao Hospital, The Third Military Medical University, Chongqing, Sichuan 400037, P.R. China, Department of Geriatrics, Kunming General Hospital of Chengdu Military Command, Kunming, Yunnan 650032, P.R. China, Department of Vascular Surgery, Kunming General Hospital of Chengdu Military Command, Kunming, Yunnan 650032, P.R. China
Published online on: September 13, 2016 https://doi.org/10.3892/ijmm.2016.2734
Pages: 1549-1557

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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.

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