2. Academic Validation
  3. YAP nuclear translocation induced by HIF-1α prevents DNA damage under hypoxic conditions

YAP nuclear translocation induced by HIF-1α prevents DNA damage under hypoxic conditions

  • Cell Death Discov. 2023 Oct 20;9(1):385. doi: 10.1038/s41420-023-01687-5.
Heng-Ai Chang 1,  Rui-Zhi Ou Yang 2,  Jing-Ming Su 2,  Thi My Hang Nguyen 2,  Junne-Ming Sung 3 4,  Ming-Jer Tang 5 6,  Wen-Tai Chiu 7 8 9
Affiliations

Affiliations

  • 1 Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, 701, Taiwan, ROC.
  • 2 Department of Biomedical Engineering, National Cheng Kung University, Tainan, 701, Taiwan, ROC.
  • 3 Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, 701, Taiwan, ROC.
  • 4 Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan, ROC.
  • 5 Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan, ROC.
  • 6 International Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan, 701, Taiwan, ROC.
  • 7 Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, 701, Taiwan, ROC. wtchiu@mail.ncku.edu.tw.
  • 8 Department of Biomedical Engineering, National Cheng Kung University, Tainan, 701, Taiwan, ROC. wtchiu@mail.ncku.edu.tw.
  • 9 Medical Device Innovation Center, National Cheng Kung University, Tainan, 701, Taiwan, ROC. wtchiu@mail.ncku.edu.tw.
PMID: 37863897 DOI: 10.1038/s41420-023-01687-5
Abstract

Maladaptive repair of acute kidney injury (AKI) is associated with a high risk of developing chronic kidney disease deemed irremediable even in present days. When AKI arises from ischemia-reperfusion injury, hypoxia usually plays a major role. Although both hypoxia-inducible factor-1α (HIF-1α) and yes-associated protein (YAP) have been proven to promote renal cell survival under hypoxia, there is a lack of research that studies the crosstalk of the two and its effect on kidney repair. In studying the crosstalk, CoCl2 was used to create a mimetic hypoxic environment. Immunoprecipitation and proximity ligation assays were performed to verify protein interactions. The results show that HIF-1α interacts with YAP and promotes nuclear translocation of YAP at a high cell density under hypoxic conditions, suggesting HIF-1α serves as a direct carrier that enables YAP nuclear translocation. This is the first study to identify HIF-1α as a crucial pathway for YAP nuclear translocation under hypoxic conditions. Once translocated into a nucleus, YAP protects cells from DNA damage and Apoptosis under hypoxic conditions. Since it is unlikely for YAP to translocate into a nucleus without HIF-1α, any treatment that fosters the crosstalk between the two holds the potential to improve cell recovery from hypoxic insults.

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