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.
Department of Bioscience, KRIBB School, University of Science & Technology, 113 Gwahak-ro, Yuseong-gu, Taejon, 34113, Republic of Korea.
Angiogenesis. 2019 May;22(2):281-293. doi: 10.1007/s10456-018-9656-z. Epub 2018 Nov 23.
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.
睾丸特异性蛋白，Y 编码样（TSPYL）家族蛋白（TSPYL1-6），属于核小体装配蛋白超家族成员，已被确定参与调节各种细胞功能。然而，TSPYL 家族蛋白在血管内皮细胞（ECs）中的潜在作用尚未确定。在这里，我们证明 TSPYL5 在人脐静脉内皮细胞（HUVECs）和人多能干细胞分化的 ECs（hPSC-ECs）等人类 ECs 中高度富集表达。重要的是，TSPYL5 的过表达通过下调 p53 表达来促进 EC 的增殖和功能，如迁移和管形成。TSPYL5 的过表达显著阻断阿霉素诱导的衰老。此外，TSPYL5 耗竭介导的 EC 功能丧失可被 p53 抑制阻断。重要的是，TSPYL5 的过表达促进了 Matrigel 塞子中的血管生成和小鼠皮肤伤口愈合模型中的伤口修复。我们的结果表明，TSPYL5 作为一种新型的血管生成调节剂，在维持内皮细胞完整性和功能方面发挥着关键作用。这些发现扩展了对 TSPYL5 依赖性机制的理解，这些机制调节了 ECs 中与 p53 相关的功能。
