Plasmolipin deficiency is essential for HUVECs survival under hypoxic conditions

Abstract This study aims to explore the molecules that affect the survival of Human Umbilical Vein Endothelial Cells (HUVECs) under hypoxia and their mechanisms of action. In hypoxia, plasmolipin (PLLP) was identified through the screening of CRISPR/Cas9 and small guide RNA (sgRNA) library. Function...

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Main Authors: Yanghua Li, Weiling Man, Xiang Li, Xiaojie Wu, Yumeng Cui, Shiyun Chen, Xianhong Li, Yanli Lin, Lihe Jiang, Youliang Wang
Format: Article
Language:English
Published: Nature Publishing Group 2025-05-01
Series:Cell Death Discovery
Online Access:https://doi.org/10.1038/s41420-025-02526-5
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author Yanghua Li
Weiling Man
Xiang Li
Xiaojie Wu
Yumeng Cui
Shiyun Chen
Xianhong Li
Yanli Lin
Lihe Jiang
Youliang Wang
author_facet Yanghua Li
Weiling Man
Xiang Li
Xiaojie Wu
Yumeng Cui
Shiyun Chen
Xianhong Li
Yanli Lin
Lihe Jiang
Youliang Wang
author_sort Yanghua Li
collection DOAJ
description Abstract This study aims to explore the molecules that affect the survival of Human Umbilical Vein Endothelial Cells (HUVECs) under hypoxia and their mechanisms of action. In hypoxia, plasmolipin (PLLP) was identified through the screening of CRISPR/Cas9 and small guide RNA (sgRNA) library. Functionally, PLLP knockout led to increase cell proliferation, cellular metabolism, tight junction formation, angiogenesis ability, migration and invasion in hypoxic HUVECs. Furthermore, PLLP knockout countered the inhibitory effects of bevacizumab on HUVECs angiogenesis and cell survival in hypoxic conditions. PLLP knockout was found to modulate the survival of HUVECs in hypoxia by enhancing the phosphorylation of AKT and ERK1/2 proteins. In conclusion, inhibiting the expression of PLLP in HUVECs promotes cell survival and maintenance of cellular functions under hypoxic condition. PLLP plays a crucial role in regulating cell survival in hypoxia through the activation of AKT and ERK1/2 pathways. This study identifies novel molecules that affect HUVECs survival under hypoxic conditions and provides a new possibility for future studies on cell survival under hypoxic conditions.
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id doaj-art-4f71a9520e694b61bf4b2a5e0d98c13f
institution DOAJ
issn 2058-7716
language English
publishDate 2025-05-01
publisher Nature Publishing Group
record_format Article
series Cell Death Discovery
spelling doaj-art-4f71a9520e694b61bf4b2a5e0d98c13f2025-08-20T03:10:13ZengNature Publishing GroupCell Death Discovery2058-77162025-05-0111111410.1038/s41420-025-02526-5Plasmolipin deficiency is essential for HUVECs survival under hypoxic conditionsYanghua Li0Weiling Man1Xiang Li2Xiaojie Wu3Yumeng Cui4Shiyun Chen5Xianhong Li6Yanli Lin7Lihe Jiang8Youliang Wang9Medical College, Guangxi UniversityLaboratory of Advanced Biotechnology, Beijing Institute of BiotechnologyLaboratory of Advanced Biotechnology, Beijing Institute of BiotechnologyLaboratory of Advanced Biotechnology, Beijing Institute of BiotechnologyLaboratory of Advanced Biotechnology, Beijing Institute of BiotechnologyLaboratory of Advanced Biotechnology, Beijing Institute of BiotechnologyLaboratory of Advanced Biotechnology, Beijing Institute of BiotechnologyLaboratory of Advanced Biotechnology, Beijing Institute of BiotechnologyMedical College, Guangxi UniversityLaboratory of Advanced Biotechnology, Beijing Institute of BiotechnologyAbstract This study aims to explore the molecules that affect the survival of Human Umbilical Vein Endothelial Cells (HUVECs) under hypoxia and their mechanisms of action. In hypoxia, plasmolipin (PLLP) was identified through the screening of CRISPR/Cas9 and small guide RNA (sgRNA) library. Functionally, PLLP knockout led to increase cell proliferation, cellular metabolism, tight junction formation, angiogenesis ability, migration and invasion in hypoxic HUVECs. Furthermore, PLLP knockout countered the inhibitory effects of bevacizumab on HUVECs angiogenesis and cell survival in hypoxic conditions. PLLP knockout was found to modulate the survival of HUVECs in hypoxia by enhancing the phosphorylation of AKT and ERK1/2 proteins. In conclusion, inhibiting the expression of PLLP in HUVECs promotes cell survival and maintenance of cellular functions under hypoxic condition. PLLP plays a crucial role in regulating cell survival in hypoxia through the activation of AKT and ERK1/2 pathways. This study identifies novel molecules that affect HUVECs survival under hypoxic conditions and provides a new possibility for future studies on cell survival under hypoxic conditions.https://doi.org/10.1038/s41420-025-02526-5
spellingShingle Yanghua Li
Weiling Man
Xiang Li
Xiaojie Wu
Yumeng Cui
Shiyun Chen
Xianhong Li
Yanli Lin
Lihe Jiang
Youliang Wang
Plasmolipin deficiency is essential for HUVECs survival under hypoxic conditions
Cell Death Discovery
title Plasmolipin deficiency is essential for HUVECs survival under hypoxic conditions
title_full Plasmolipin deficiency is essential for HUVECs survival under hypoxic conditions
title_fullStr Plasmolipin deficiency is essential for HUVECs survival under hypoxic conditions
title_full_unstemmed Plasmolipin deficiency is essential for HUVECs survival under hypoxic conditions
title_short Plasmolipin deficiency is essential for HUVECs survival under hypoxic conditions
title_sort plasmolipin deficiency is essential for huvecs survival under hypoxic conditions
url https://doi.org/10.1038/s41420-025-02526-5
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AT xiaojiewu plasmolipindeficiencyisessentialforhuvecssurvivalunderhypoxicconditions
AT yumengcui plasmolipindeficiencyisessentialforhuvecssurvivalunderhypoxicconditions
AT shiyunchen plasmolipindeficiencyisessentialforhuvecssurvivalunderhypoxicconditions
AT xianhongli plasmolipindeficiencyisessentialforhuvecssurvivalunderhypoxicconditions
AT yanlilin plasmolipindeficiencyisessentialforhuvecssurvivalunderhypoxicconditions
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