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Protein Disulfide Isomerase 4 Is an Essential Regulator of Endothelial Function and Survival.


ABSTRACT: Endothelial autophagy plays an important role in the regulation of endothelial function. The inhibition of endothelial autophagy is associated with the reduced expression of protein disulfide isomerase 4 (PDIA-4); however, its role in endothelial cells is not known. Here, we report that endothelial cell-specific loss of PDIA-4 leads to impaired autophagic flux accompanied by loss of endothelial function and apoptosis. Endothelial cell-specific loss of PDIA-4 also induced marked changes in endothelial cell architecture, accompanied by the loss of endothelial markers and the gain of mesenchymal markers consistent with endothelial-to-mesenchymal transition (EndMT). The loss of PDIA-4 activated TGFβ-signaling, and inhibition of TGFβ-signaling suppressed EndMT in PDIA-4-silenced endothelial cells in vitro. Our findings help elucidate the role of PDIA-4 in endothelial autophagy and endothelial function and provide a potential target to modulate endothelial function and/or limit autophagy and EndMT in (patho-)physiological conditions.

SUBMITTER: Bu S 

PROVIDER: S-EPMC11011381 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Protein Disulfide Isomerase 4 Is an Essential Regulator of Endothelial Function and Survival.

Bu Shuhan S   Singh Aman A   Nguyen Hien C HC   Peddi Bharatsinai B   Bhatt Kriti K   Ravendranathan Naresh N   Frisbee Jefferson C JC   Singh Krishna K KK  

International journal of molecular sciences 20240331 7


Endothelial autophagy plays an important role in the regulation of endothelial function. The inhibition of endothelial autophagy is associated with the reduced expression of <i>protein disulfide isomerase 4</i> (<i>PDIA-4</i>); however, its role in endothelial cells is not known. Here, we report that endothelial cell-specific loss of PDIA-4 leads to impaired autophagic flux accompanied by loss of endothelial function and apoptosis. Endothelial cell-specific loss of PDIA-4 also induced marked cha  ...[more]

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