Substance P-Mediated Expression of the Pro-Angiogenic Factor CCN1 Modulates the Course of Colitis
Open accessAbstract
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 alphavbeta3. 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.
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CCN1 is upregulated in patients with Crohn's disease and ulcerative colitis.
“CCN1 is upregulated in patients with Crohn’s disease and ulcerative colitis, and in colons of mice treated with dextran sodium sulfate to induce inflammatory colitis [132].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [132]
CCN1 is upregulated in colons of mice treated with dextran sodium sulfate to induce inflammatory colitis.
“CCN1 is upregulated in patients with Crohn’s disease and ulcerative colitis, and in colons of mice treated with dextran sodium sulfate to induce inflammatory colitis [132].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [132]
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CCN1/CYR61: the very model of a modern matricellular protein
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- Authors
- Koon, H.-W., Zhao, D., Xu, H., Bowe, C., Moss, A., Moyer, M. P., & Pothoulakis, C.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Incell Corporation (United States) (US)
- Corresponding author
- Pothoulakis, Charalabos
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2008-08
- Volume
- 173
- Issue
- 2
- Pages
- 400-410
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC2475777
- OpenAlex
- W2078535342
- Cited by
- 41
- References
- 49
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2019: 2 · 2018: 1 · 2017: 5 · 2016: 1 · 2015: 6 · 2014: 6 · 2013: 1 · 2012: 1
- FWCI
- 2.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Crohn's and Colitis Foundation of America
- National Institutes of Health (DK 47343)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
- Keywords
- substance P, CYR61, angiogenesis, colitis, neurokinin-1 receptor, inflammatory bowel disease, Crohn's disease, ulcerative colitis, integrin αvβ3, endothelial cell migration, DSS-induced colitis, intestinal microvasculature
- MeSH terms
- Animals, Cell Movement, Colitis, Ulcerative, Colon, Crohn Disease, Endothelium, Vascular, Humans, Male, Mice, Inbred C57BL, Microcirculation, Neovascularization, Pathologic, Substance P, Dextran Sulfate, Immediate-Early Proteins, Receptors, Neurokinin-1, Bridged Bicyclo Compounds, Heterocyclic, Intercellular Signaling Peptides and Proteins, Integrin alphaVbeta3, Endothelial Cells, Mice, Cysteine-Rich Protein 61
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