Corticotropin Releasing Hormone and Urocortin 3 Stimulate Vascular Endothelial Growth Factor Expression through the cAMP/CREB Pathway.

The Journal of Biological Chemistry
Sang Hoon RheeEunok Im

Abstract

Colonic epithelium is the first line of defense against various pathological offenses in the gut. Previous studies have shown that the peptides of the corticotropin-releasing hormone (CRH) family modulate vascular endothelial growth factor (VEGF)-A production in other cells. Here we sought to investigate whether CRH and urocortin (Ucn) 3 regulate VEGF-A secretion in colonocytes through CRH receptors and to elucidate the underlying mechanism of action. CRH and Ucn 3 significantly increased the expression levels of VEGF-A mRNA and protein through CRH receptor 1 and 2, respectively, in human colonic epithelial cells and primary mouse intestinal epithelial cells. Underlying mechanisms involve activation of adenylyl cyclase with subsequent increase of intracellular cAMP level and increased DNA binding activity of transcription factor CREB on VEGF-A promoter region. Finally, genetic deficiency of CREB decreased intestinal inflammation and VEGF-A expression in a dextran sodium sulfate-induced colitis model. These results show that activation of CRH receptors by CRH ligands stimulates VEGF-A expression in intestinal epithelial cells through the cAMP/CREB pathway. Since VEGF-A boosts inflammatory responses through angiogenesis, these da...Continue Reading

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Citations

Jul 28, 2016·Biochemical and Biophysical Research Communications·Chaowen HuangShaoxi Cai
Apr 4, 2021·International Journal of Molecular Sciences·Yasuo YoshitomiHideto Yonekura
Jun 5, 2021·World Journal of Gastrointestinal Pathophysiology·Surbhi AggarwalJaishree Paul
Aug 28, 2021·International Journal of Molecular Sciences·Shao-Chun WuChing-Hua Hsieh

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