Hypoxia-inducible factor/MAZ-dependent induction of caveolin-1 regulates colon permeability through suppression of occludin, leading to hypoxia-induced inflammation

Liwei Xie, Xiang Xue, Matthew Taylor, Sadeesh K. Ramakrishnan, Kenjiro Nagaoka, Cathy Hao, Frank J. Gonzalez, Yatrik M. Shah

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Caveolae are specialized microdomains on membranes that are critical for signal transduction, cholesterol transport, and endocytosis. Caveolin-1 (CAV1) is a multifunctional protein and a major component of caveolae. Cav1 is directly activated by hypoxia-inducible factor (HIF). HIFs are heterodimers of an oxygen-sensitive α subunit, HIF1α or HIF2α, and a constitutively expressed β subunit, aryl hydrocarbon receptor nuclear translocator (ARNT). Whole-genome expression analysis demonstrated that Cav1 is highly induced in mouse models of constitutively activated HIF signaling in the intestine. Interestingly, Cav1 was increased only in the colon and not in the small intestine. Currently, the mechanism and role of HIF induction of CAV1 in the colon are unclear. In mouse models, mice that overexpressed HIF1α or HIF2α specifically in intestinal epithelial cells demonstrated an increase in Cav1 gene expression in the colon but not in the duodenum, jejunum, or ileum. HIF2α activated the Cav1 promoter in a HIF response element-independent manner. myc-associated zinc finger (MAZ) protein was essential for HIF2α activation of the Cav1 promoter. Hypoxic induction of CAV1 in the colon was essential for intestinal barrier integrity by regulating occludin expression. This may provide an additional mechanism by which chronic hypoxia can activate intestinal inflammation.

Original languageEnglish
Pages (from-to)3013-3023
Number of pages11
JournalMolecular and Cellular Biology
Volume34
Issue number16
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

Occludin
Caveolin 1
Zinc Fingers
Permeability
Colon
Inflammation
Caveolae
Aryl Hydrocarbon Receptor Nuclear Translocator
Membrane Microdomains
Response Elements
Jejunum
Endocytosis
Ileum
Duodenum
Small Intestine
Intestines
Signal Transduction
Proteins
Epithelial Cells
Cholesterol

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Hypoxia-inducible factor/MAZ-dependent induction of caveolin-1 regulates colon permeability through suppression of occludin, leading to hypoxia-induced inflammation. / Xie, Liwei; Xue, Xiang; Taylor, Matthew; Ramakrishnan, Sadeesh K.; Nagaoka, Kenjiro; Hao, Cathy; Gonzalez, Frank J.; Shah, Yatrik M.

In: Molecular and Cellular Biology, Vol. 34, No. 16, 2014, p. 3013-3023.

Research output: Contribution to journalArticle

Xie, Liwei ; Xue, Xiang ; Taylor, Matthew ; Ramakrishnan, Sadeesh K. ; Nagaoka, Kenjiro ; Hao, Cathy ; Gonzalez, Frank J. ; Shah, Yatrik M. / Hypoxia-inducible factor/MAZ-dependent induction of caveolin-1 regulates colon permeability through suppression of occludin, leading to hypoxia-induced inflammation. In: Molecular and Cellular Biology. 2014 ; Vol. 34, No. 16. pp. 3013-3023.
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