Over Expression of Hypoxia-Inducible Protein 2, Hypoxia-Inducible Factor-1α and Nuclear Factor κB is Putatively Involved in Acquired Renal Cyst Formation and Subsequent Tumor Transformation in Patients With End Stage Renal Failure

Abstract BACKGROUND: Aneurysmal subarachnoid hemorrhage, almost always from saccular intracranial aneurysm (sIA), is a devastating form of stroke that affects the working-age population. Cellular and molecular mechanisms predisposing to the rupture of the sIA wall are largely unknown. This knowledge would facilitate the design of novel diagnostic tools and therapies for the sIA disease. OBJECTIVE: To investigate gene expression patterns distinguishing ruptured and unruptured sIA. METHODS: We compared the whole-genome expression profile of 11 ruptured sIA wall samples with that of 8 unruptured ones using oligonucleotide microarrays. Signaling pathways enriched in the ruptured sIA walls were identified with bioinformatic analyses. Their transcriptional control was predicted in silico by seeking the enrichment of conserved transcription factor binding sites in the promoter regions of differentially expressed genes. RESULTS: Overall, 686 genes were significantly upregulated and 740 were downregulated in the ruptured sIA walls. Significantly upregulated biological processes included response to turbulent blood flow, chemotaxis, leukocyte migration, oxidative stress, vascular remodeling; and extracellular matrix degradation. Toll-like receptor signaling and nuclear factor-κB, hypoxia-inducible factor-1A, and ETS transcription factor binding sites were significantly enriched among the upregulated genes. CONCLUSION: We identified pathways and candidate genes associated with the rupture of human sIA wall. Our results may provide clues to the molecular mechanism in sIA wall rupture and insight for novel therapeutic strategies to prevent rupture.

Download Full-text

Hypoxia‐inducible factor‐1α and nuclear factor‐κB play important roles in regulating programmed cell death ligand 1 expression by epidermal growth factor receptor mutants in non‐small‐cell lung cancer cells

Cancer Science ◽

10.1111/cas.13989 ◽

2019 ◽

Vol 110 (5) ◽

pp. 1665-1675 ◽

Cited By ~ 11

Author(s):

Rong Guo ◽

Yong Li ◽

Zhijie Wang ◽

Hua Bai ◽

Jianchun Duan ◽

...

Keyword(s):

Lung Cancer ◽

Cell Death ◽

Epidermal Growth Factor Receptor ◽

Hypoxia Inducible Factor ◽

Growth Factor Receptor ◽

Nuclear Factor Κb ◽

Small Cell ◽

Nuclear Factor ◽

Small Cell Lung ◽

Epidermal Growth

Download Full-text

Hypoxia Up-Regulates Hypoxia-Inducible Factor-1α Transcription by Involving Phosphatidylinositol 3-Kinase and Nuclear Factor κB in Pulmonary Artery Smooth Muscle Cells

Molecular Biology of the Cell ◽

10.1091/mbc.e07-04-0391 ◽

2007 ◽

Vol 18 (12) ◽

pp. 4691-4697 ◽

Cited By ~ 256

Author(s):

Rachida S. BelAiba ◽

Steve Bonello ◽

Christian Zähringer ◽

Stefanie Schmidt ◽

John Hess ◽

...

Keyword(s):

Smooth Muscle ◽

Pulmonary Artery ◽

Smooth Muscle Cells ◽

Promoter Activity ◽

Hypoxia Inducible Factor ◽

Nuclear Factor Κb ◽

Mrna Levels ◽

Nuclear Factor ◽

Phosphatidylinositol 3 Kinase ◽

Pulmonary Artery Smooth Muscle

The oxygen sensitive α-subunit of the hypoxia-inducible factor-1 (HIF-1) is a major trigger of the cellular response to hypoxia. Although the posttranslational regulation of HIF-1α by hypoxia is well known, its transcriptional regulation by hypoxia is still under debate. We, therefore, investigated the regulation of HIF-1α mRNA in response to hypoxia in pulmonary artery smooth muscle cells. Hypoxia rapidly enhanced HIF-1α mRNA levels and HIF-1α promoter activity. Furthermore, inhibition of the phosphatidylinositol 3-kinase (PI3K)/AKT but not extracellular signal-regulated kinase 1/2 pathway blocked the hypoxia-dependent induction of HIF-1α mRNA and HIF-1α promoter activity, suggesting involvement of a PI3K/AKT-regulated transcription factor. Interestingly, hypoxia also induced nuclear factor-κB (NFκB) nuclear translocation and activity. In line, expression of the NFκB subunits p50 and p65 enhanced HIF-1α mRNA levels, whereas blocking of NFκB by an inhibitor of nuclear factor-κB attenuated HIF-1α mRNA induction by hypoxia. Reporter gene assays revealed the presence of an NFκB site within the HIF-1α promoter, and mutation of this site abolished induction by hypoxia. In line, gel shift analysis and chromatin immunoprecipitation confirmed binding of p50 and p65 NFκB subunits to the HIF-1α promoter under hypoxia. Together, these findings provide a novel mechanism in which hypoxia induces HIF-1α mRNA expression via the PI3K/AKT pathway and activation of NFκB.

Download Full-text