TSPYL5-mediated inhibition of p53 promotes human endothelial cell function
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.
KeywordsTSPYL5 Endothelial cells Proliferation Angiogenesis p53
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).
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.
Compliance with ethical standards
Conflict of interest
The authors have declared no potential conflicts of interest.
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