Substance P Induces CCN1 Expression via Histone Deacetylase Activity in Human Colonic Epithelial Cells

摘要: We have shown that substance P (SP) and its neurokinin-1 receptor (NK-1R) regulate intestinal angiogenesis by increasing expression of protein CYR61 (the cysteine-rich angiogenic inducer 61, or CCN1) in colonic epithelial cells. However, the mechanism involved SP-induced CCN1 has not been studied, outcome increased development colitis is fully understood. Because histone deacetylase (HDAC) modulates transcription several genes inflammation, we investigated participation HDAC human NCM460 cells overexpressing NK-1R (NCM460-NK-1R) primary colonocytes. SP activity with deacetylation dephosphorylation nucleosome H3 NCM460-NK-1R and/or Histone was observed mucosa from irritable bowel disease patients. Similarly, mucosal tissues mice exposed to dextran sulfate sodium showed reversed antagonist CJ-12255. abolished pharmacological inhibition. overexpression activated basal promoter activity. Intracolonic significantly ameliorated sodium-induced colitis, reduction proinflammatory cytokine mice. Thus, SP-mediated inflamed mouse colon involves Our results strongly suggest may be healing during colitis.