Substance P-mediated expression of the pro-angiogenic factor CCN1 modulates the course of colitis

Hon Wai Koon, Dezheng Zhao, Hua Xu, Collin Bowe, Alan Moss, Mary P. Moyer, Charalabos Pothoulakis

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Substance P (SP) regulates important intestinal functions, such as mucosal permeability, motility, chloride secretion, and inflammation via the neurokinin-1 receptor (NK-1R). Previous reports showed that vascularization and expression of angiogenic factors are evident in the colonic mucosa of rats with colitis and patients with inflammatory bowel disease. Here we determined whether SP is associated with angiogenesis. Human NCM460 colonocytes stably transfected with the human NK-1R (NCM460-NK-1R cells) and mice with dextran sodium sulfate-induced colitis were used. We found that expression of the angiogenic factor CCN1 was increased in the colons of patients with Crohn's disease and ulcerative colitis. Mucosal extracts from inflammatory bowel disease patients induced human intestinal microvascular endothelial cell migration that was inhibited by blockade of CCN1 and its receptor integrin αvβ3. Both the degree of angiogenesis and CCN1 expression were elevated in the colons of mice with dextran sodium sulfate-induced colitis , which was reduced by treatment with the NK-1R antagonist CJ-12255. SP also increased CCN1 expression in NCM460-NK-1R colonocytes. SP exposure to human intestinal microvascular endothelial cells co-cultured with NCM460-NK-1R cells induced angiogenic activity that was inhibited by CCN1 silencing. In addition, intracolonic overexpression of CCN1 induced angiogenesis in mouse colon. Thus, SP mediates angiogenesis via CCN1 during colitis.

Original languageEnglish (US)
Pages (from-to)400-410
Number of pages11
JournalAmerican Journal of Pathology
Volume173
Issue number2
DOIs
StatePublished - Aug 2008
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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