Distinctive Roles of YAP and TAZ in Human Endothelial Progenitor Cells Growth and Functions
The hippo signaling pathway plays an essential role in controlling organ size and balancing tissue homeostasis. Its two main effectors, yes-associated protein (YAP) and WW domain-containing transcription regulator 1, WWTR1 or TAZ, have also been shown to regulate endothelial cell functions and angio...
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MDPI AG
2022-01-01
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| Online Access: | https://www.mdpi.com/2227-9059/10/1/147 |
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| author | Phatchanat Klaihmon Chanchao Lorthongpanich Pakpoom Kheolamai Sudjit Luanpitpong Surapol Issaragrisil |
| author_facet | Phatchanat Klaihmon Chanchao Lorthongpanich Pakpoom Kheolamai Sudjit Luanpitpong Surapol Issaragrisil |
| author_sort | Phatchanat Klaihmon |
| collection | DOAJ |
| description | The hippo signaling pathway plays an essential role in controlling organ size and balancing tissue homeostasis. Its two main effectors, yes-associated protein (YAP) and WW domain-containing transcription regulator 1, WWTR1 or TAZ, have also been shown to regulate endothelial cell functions and angiogenesis. In this study, the functions of YAP and TAZ in human endothelial progenitor cells (EPCs) were investigated by a loss-of-function study using CRISPR/Cas9-mediated gene knockdown (KD). Depletion of either YAP or TAZ reduced EPC survival and impaired many of their critical functions, including migration, invasion, vessel-formation, and expression of pro-angiogenic genes. Notably, TAZ-KD EPCs exhibited more severe phenotypes in comparison to YAP-KD EPCs. Moreover, the conditioned medium derived from TAZ-KD EPCs reduced the survivability of human lung cancer cells and increased their sensitivity to chemotherapeutic agents. The overexpression of either wild-type or constitutively active TAZ rescued the impaired phenotypes of TAZ-KD EPCs and restored the expression of pro-angiogenic genes in those EPCs. In summary, we demonstrate the crucial role of Hippo signaling components, YAP and TAZ, in controlling several aspects of EPC functions that can potentially be used as a drug target to enhance EPC functions in patients. |
| first_indexed | 2024-03-10T01:52:26Z |
| format | Article |
| id | doaj.art-eae58890544d46fe99d03903b9880423 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T01:52:26Z |
| publishDate | 2022-01-01 |
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| spelling | doaj.art-eae58890544d46fe99d03903b98804232023-11-23T13:04:35ZengMDPI AGBiomedicines2227-90592022-01-0110114710.3390/biomedicines10010147Distinctive Roles of YAP and TAZ in Human Endothelial Progenitor Cells Growth and FunctionsPhatchanat Klaihmon0Chanchao Lorthongpanich1Pakpoom Kheolamai2Sudjit Luanpitpong3Surapol Issaragrisil4Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ThailandSiriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ThailandCenter of Excellence in Stem Cell Research and Innovation, Faculty of Medicine, Thammasat University, Pathum Thani 12120, ThailandSiriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ThailandSiriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ThailandThe hippo signaling pathway plays an essential role in controlling organ size and balancing tissue homeostasis. Its two main effectors, yes-associated protein (YAP) and WW domain-containing transcription regulator 1, WWTR1 or TAZ, have also been shown to regulate endothelial cell functions and angiogenesis. In this study, the functions of YAP and TAZ in human endothelial progenitor cells (EPCs) were investigated by a loss-of-function study using CRISPR/Cas9-mediated gene knockdown (KD). Depletion of either YAP or TAZ reduced EPC survival and impaired many of their critical functions, including migration, invasion, vessel-formation, and expression of pro-angiogenic genes. Notably, TAZ-KD EPCs exhibited more severe phenotypes in comparison to YAP-KD EPCs. Moreover, the conditioned medium derived from TAZ-KD EPCs reduced the survivability of human lung cancer cells and increased their sensitivity to chemotherapeutic agents. The overexpression of either wild-type or constitutively active TAZ rescued the impaired phenotypes of TAZ-KD EPCs and restored the expression of pro-angiogenic genes in those EPCs. In summary, we demonstrate the crucial role of Hippo signaling components, YAP and TAZ, in controlling several aspects of EPC functions that can potentially be used as a drug target to enhance EPC functions in patients.https://www.mdpi.com/2227-9059/10/1/147hippo signaling pathwayendothelial progenitor cellsYAP/TAZ |
| spellingShingle | Phatchanat Klaihmon Chanchao Lorthongpanich Pakpoom Kheolamai Sudjit Luanpitpong Surapol Issaragrisil Distinctive Roles of YAP and TAZ in Human Endothelial Progenitor Cells Growth and Functions Biomedicines hippo signaling pathway endothelial progenitor cells YAP/TAZ |
| title | Distinctive Roles of YAP and TAZ in Human Endothelial Progenitor Cells Growth and Functions |
| title_full | Distinctive Roles of YAP and TAZ in Human Endothelial Progenitor Cells Growth and Functions |
| title_fullStr | Distinctive Roles of YAP and TAZ in Human Endothelial Progenitor Cells Growth and Functions |
| title_full_unstemmed | Distinctive Roles of YAP and TAZ in Human Endothelial Progenitor Cells Growth and Functions |
| title_short | Distinctive Roles of YAP and TAZ in Human Endothelial Progenitor Cells Growth and Functions |
| title_sort | distinctive roles of yap and taz in human endothelial progenitor cells growth and functions |
| topic | hippo signaling pathway endothelial progenitor cells YAP/TAZ |
| url | https://www.mdpi.com/2227-9059/10/1/147 |
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