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Id1 modulates endothelial progenitor cells function through relieving the E2-2-mediated repression of FGFR1 and VEGFR2 in vitro

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Abstract

The migration and proliferation of EPCs are crucial for re-endothelialization in vascular repair and development. Id1 has a regulatory role in the regulation of EPCs migration and proliferation. Based on these findings, we hypothesized that Id1 plays a regulatory role in modulating the migration and proliferation of EPCs by interaction with other factors. Herein, we report that the Id1 protein and E-box protein E2-2 regulate EPCs function with completely opposite effects. Id1 plays a positive role in the regulation of EPC proliferation and migration, while endogenous E2-2 appears to be a negative regulator. Immunoprecipitation and immunofluorescence assay revealed that the Id1 protein interacts and co-localizes with the E2-2 protein in EPCs. Further, endogenous E2-2 protein was found to block EPCs function via the inhibition of FGFR1 and VEGFR2 expression. The overexpression and silencing of Id1 have no direct regulatory role on VEGFR2 and FGFR1 expression. On the other hand, Id1 relieves the E2-2-mediated repression of FGFR1 and VEGFR2 expression to modulate EPCs proliferation, migration, and tube formation in vitro. In summary, we demonstrated that Id1 and E2-2 are critical regulators of EPCs function in vitro. Id1 interacts with E2-2 and relieves the E2-2-mediated repression of FGFR1 and VEGFR2 expression to modulate EPCs functions. Id1 and E2-2 may represent novel therapeutic targets for re-endothelialization in vascular damage and repair.

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Acknowledgments

This research was supported by the National Natural Science Foundation of China (Grant No. 81270224).

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    Authors and Affiliations

    1. Cardiologic Center of PLA, Xin Qiao Hospital, Third Military Medical University, Chongqing, 400037, China

      Yang Yu

    2. Geriatric Department, Kunming General Hospital of Chengdu Military Command, Daguan Road No. 212, Kunming, 650032, China

      Yuan Liang, Xiaoli Liu, Haijie Yang, Yong Su, Xi Xia & Hong Wang

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    1. Yang Yu
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    2. Yuan Liang
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    3. Xiaoli Liu
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    4. Haijie Yang
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    7. Hong Wang
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    Correspondence to Hong Wang.

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    Yang Yu and Yuan Liang have contributed equally to this work.

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    Yu, Y., Liang, Y., Liu, X. et al. Id1 modulates endothelial progenitor cells function through relieving the E2-2-mediated repression of FGFR1 and VEGFR2 in vitro. Mol Cell Biochem 411, 289–298 (2016). https://doi.org/10.1007/s11010-015-2591-z

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