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TSPYL5-mediated inhibition of p53 promotes human endothelial cell function

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Abstract

Testis-specific protein, Y-encoded like (TSPYL) family proteins (TSPYL1-6), which are members of the nucleosome assembly protein superfamily, have been determined to be involved in the regulation of various cellular functions. However, the potential role of TSPYL family proteins in endothelial cells (ECs) has not been determined. Here, we demonstrated that the expression of TSPYL5 is highly enriched in human ECs such as human umbilical vein endothelial cells (HUVECs) and human pluripotent stem cell-differentiated ECs (hPSC-ECs). Importantly, TSPYL5 overexpression was shown to promote EC proliferation and functions, such as migration and tube formation, by downregulating p53 expression. Adriamycin-induced senescence was markedly blocked by TSPYL5 overexpression. In addition, the TSPYL5 depletion-mediated loss of EC functions was blocked by p53 inhibition. Significantly, TSPYL5 overexpression promoted angiogenesis in Matrigel plug and wound repair in a mouse skin wound healing model in vivo. Our results suggest that TSPYL5, a novel angiogenic regulator, plays a key role in maintaining endothelial integrity and function. These findings extend the understanding of TSPYL5-dependent mechanisms underlying the regulation of p53-related functions in ECs.

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Acknowledgements

This work was supported by National Research Foundation of Korea (NRF) (Grant No. 2017R1A2B2012190) and NST (Grant No. CRC-15-02-KRIBB) grants from the Korean government (MSIP).

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  1. Hee-Jun Na, Chung Eun Yeum and Han-Seop Kim have contributed equally to this work.

Authors and Affiliations

  1. Stem Cell Research Laboratory, Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Taejon, 34141, Republic of Korea

    Hee-Jun Na, Chung Eun Yeum, Han-Seop Kim, Jungwoon Lee, Jae Yun Kim & Yee Sook Cho

  2. Department of Bioscience, KRIBB School, University of Science & Technology, 113 Gwahak-ro, Yuseong-gu, Taejon, 34113, Republic of Korea

    Jae Yun Kim & Yee Sook Cho

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  1. Hee-Jun Na
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Contributions

H-JN: Conception and design, data analysis and interpretation, manuscript writing, final approval of manuscript. CEY: Conception and design, data analysis and interpretation, manuscript writing, final approval of manuscript. H-SK: Collection and assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript. JL: Conception and design, data analysis and interpretation. J-YK: Collection and assembly of data, manuscript writing. YSC: Conception and design, data analysis and interpretation, financial support, manuscript writing, final approval of manuscript.

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Correspondence to Yee Sook Cho.

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Na, HJ., Yeum, C.E., Kim, HS. et al. TSPYL5-mediated inhibition of p53 promotes human endothelial cell function. Angiogenesis 22, 281–293 (2019). https://doi.org/10.1007/s10456-018-9656-z

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  • DOI: https://doi.org/10.1007/s10456-018-9656-z

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