Aim: Hypoxia-inducible factor-2α (HIF-2α) has been reported to play an important role in a host of pathophysiological processes, including cellular survival. This study explores the role of HIF-2α in cholestasis-mediated hepatocyte apoptosis.
Methods: Hypoxia-inducible factor-2α expression was measured by immunohistochemistry and confocal microscopy. Hepatic apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling. The cholestatic mouse model was treated with bile duct ligation. The c-myc, p53, and Bax protein levels were measured with Western blot analysis.
Results: In pediatric and murine cholestatic liver tissues, HIF-2α protein was widely expressed in the nucleus of parenchymal cells as well as in stromal cells. Hepatocyte HIF-2α expression was significantly elevated at the early stage of pediatric cholestasis and decreased at the late stage. In both in vivo and in vitro murine studies, HIF-2α deletion could alleviate cholestasis-mediated hepatocyte apoptosis and regulate the expression of c-myc, p53, and Bax proteins.
Conclusion: These findings implied the contribution of HIF-2α to cholestasis-mediated hepatocyte apoptosis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/hepr.12708 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
HIF-1α mediates hypertension and vascular remodeling in sleep apnea via hippo-YAP pathway activation.
Mol Med
December 2024
Department of Otorhinolaryngology/Head and Neck, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No.3 East Qingchun Road, Hangzhou, 310020, Zhejiang, China.
Background: Sleep apnea syndrome (SAS) is associated with hypertension and vascular remodeling. Hypoxia-inducible factor-1α (HIF-1α) and the Hippo-YAP pathway are implicated in these processes, but their specific roles remain unclear. This study investigated the HIF-1α/Hippo-YAP pathway in SAS-related hypertension.
View Article and Find Full Text PDFDaphnetin may protect from SARS-CoV-2 infection by reducing ACE2.
Sci Rep
December 2024
School of Preclinical Medicine, Wannan Medical College, Wuhu, 241002, China.
To combat the SARS-CoV-2 pandemic, innovative prevention strategies are needed, including reducing ACE2 expression on respiratory cells. This study screened approved drugs in China for their ability to downregulate ACE2. Daphnetin (DAP) was found to significantly reduce ACE2 mRNA and protein levels in PC9 cells.
View Article and Find Full Text PDFAdipocyte-derived ferroptotic signaling mitigates obesity.
Cell Metab
December 2024
The Second Affiliated Hospital, School of Public Health, State Key Laboratory of Experimental Hematology, Zhejiang University School of Medicine, Hangzhou 310058, China; School of Public Health, Basic Medical Sciences, School of Pharmacology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, China; School of Public Health, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, China. Electronic address:
Ferroptosis is characterized as an iron-dependent and lipophilic form of cell death. However, it remains unclear what role ferroptosis has in adipose tissue function and activity. Here, we find a lower ferroptotic signature in the adipose tissue of individuals and mice with obesity.
View Article and Find Full Text PDFTumor-targeted nanosystem with hypoxia inducible factor 1α inhibition for synergistic chemo-photodynamic therapy against hypoxic tumor.
Colloids Surf B Biointerfaces
December 2024
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; National Innovation Platform for medical industry-education integration, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address:
Photodynamic therapy (PDT) holds an essential role in the therapy of tumors. However, PDT consumes tissue oxygen and diminishes its own efficacy by inducing tumor hypoxia through the HIF-1α/VEGF pathway. Therefore, overcoming the photodynamic exacerbation of tumor hypoxia could reverse tumor microenvironment and enhance PDT.
View Article and Find Full Text PDFTIPE drives a cancer stem-like phenotype by promoting glycolysis via PKM2/HIF-1α axis in melanoma.
Elife
December 2024
Center of Translational Medicine, Zibo Central Hospital Affiliated to Binzhou Medical University, Zibo, China.
TIPE () has been identified as an oncogene and participates in tumor biology. However, how its role in the metabolism of tumor cells during melanoma development remains unclear. Here, we demonstrated that TIPE promoted glycolysis by interacting with pyruvate kinase M2 (PKM2) in melanoma.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!