Basic—Alimentary TractCorticotropin-Releasing Hormone Family of Peptides Regulates Intestinal Angiogenesis
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Animal Models
CRHR1 heterozygote mice (Crhr1tm1Klee) were obtained from The Jackson Laboratory. CRHR1-deficient mice and their wild-type littermates (M&F, 8–12 weeks) were derived from heterozygous breedings. CRHR2-deficient mice were a gift from Dr W. Vale (Salk Institute, La Jolla, CA) and had been backcrossed onto a B6 background (>N10). CRHR2-deficient mice and their wild-type littermates (M&F, 8–12 weeks) were derived from heterozygous breedings. To induce colitis, mice were fed with DSS (4%, MP
Genetic Deficiency of CRHR1 Ameliorates, but CRHR2 Deficiency Exacerbates Intestinal Inflammation
We first determined the differential function of CRHR1 and CRHR2 in intestinal inflammation. CRHR1−/−, CRHR2−/−, and their littermate control mice were subjected to DSS-induced colitis for 14 days and the inflammatory response was evaluated. Mortality and weight loss were reduced in CRHR1−/− mice compared with their littermate control CRHR1+/+ mice (Figure 1A and B). In contrast, mortality and weight loss were increased in CRHR2−/− mice compared with their littermate control CRHR2+/+ mice (
CRH Family of Peptides Differentially Regulates Intestinal Angiogenesis
Here we identify what we believe to be a novel function for the CRH family of peptides as a regulator of angiogenesis in the inflamed intestine. Our first indication that endogenous CRH might be proangiogenic came from studies in mice with global deletion of CRHR1 that showed severely delayed vessel outgrowth from aortic explants. CRH is densely expressed on SMCs in the vascular system15 and CRH-producing tumor cells significantly enhance angiogenesis when injected subcutaneously into nude mice,
References (40)
- et al.
Angiogenesis as a novel component of inflammatory bowel disease pathogenesis
Gastroenterology
(2006) - et al.
VEGF, basic-FGF, and TGF-beta in Crohn's disease and ulcerative colitis: a novel mechanism of chronic intestinal inflammation
Am J Gastroenterol
(2001) - et al.
Urocortin and corticotropin-releasing factor receptor expression in the human colonic mucosa
Peptides
(2000) - et al.
Enhanced leukocyte binding by intestinal microvascular endothelial cells in inflammatory bowel disease
Gastroenterology
(1997) Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: antibiotics, probiotics, and prebiotics
Gastroenterology
(2004)- et al.
Altered angiogenic balance in ulcerative colitis: a key to impaired healing?
Biochem Biophys Res Commun
(2006) - et al.
Corticotropin-releasing hormone stimulates angiogenesis and epithelial tumor growth in the skin
J Invest Dermatol
(1999) - et al.
Corticotropin-releasing hormone antagonists possess anti-inflammatory effects in the mouse ileum
Gastroenterology
(2002) - et al.
Urocortin 2 expression in the rat gastrointestinal tract under basal conditions and in chemical colitis
Peptides
(2007) - et al.
Angiogenic effects of interleukin 8 (CXCL8) in human intestinal microvascular endothelial cells are mediated by CXCR2
J Biol Chem
(2003)
The codependence of angiogenesis and chronic inflammation
FASEB J
Angiogenesis blockade as a new therapeutic approach to experimental colitis
Gut
Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin
Science
Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor
Proc Natl Acad Sci U S A
Urocortin II: a member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by type 2 CRF receptors
Proc Natl Acad Sci U S A
Human stresscopin and stresscopin-related peptide are selective ligands for the type 2 corticotropin-releasing hormone receptor
Nat Med
The molecular mechanisms underlying the regulation of the biological activity of corticotropin-releasing hormone receptors: implications for physiology and pathophysiology
Endocr Rev
Corticotropin-releasing factor receptors and stress-related alterations of gut motor function
J Clin Invest
Corticotropin-releasing hormone (CRH) requirement in Clostridium difficile toxin A-mediated intestinal inflammation
Proc Natl Acad Sci U S A
Corticotropin-releasing hormone receptor 2-deficient mice have reduced intestinal inflammatory responses
J Immunol
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Conflicts of interest The authors disclose no conflicts.
Funding This work was supported by a Young Clinical Scientist Award from “FAMRI, Inc.” (EI and SHR) and by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney DiseasesKO1 DK083336 (EI), KO1 DK079015 (SHR), RO1 DK50894, and RO1 DK69854 (CF), VA Career Scientist Award and DK41301 (YT), and PO1 DK33506 and RO1 DK072471 (CP).