Author(s): Matkowskyj KA, Nathaniel R, Prasad R, Weihrauch D, Rao M,
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Abstract Galanin is present in enteric nerves lining the gastrointestinal (GI) tract where it is normally involved in regulating intestinal motility by binding to the galanin-1 receptor (Gal1R) subtype expressed by smooth muscle cells. In contrast, although epithelial cells lining the colon do not normally express Gal1R, this protein is up-regulated by the inflammation-associated transcription factor NF-kappaB. We previously showed that the murine colitis induced by dextran sulfate sodium (DSS) was associated with increased Gal1R expression as well as by increased colonic fluid secretion. Although Gal1R up-regulation by colonic epithelial cells results in increased intestinal Cl- secretion, the relative contributions of galanin to this excess colonic fluid secretion could not be determined. We therefore created a mouse genetically incapable of synthesizing Gal1R (GAL1R-/- mice). We herein demonstrate that both wild-type and GAL1R-/- mice developed identical histologic lesions in response to DSS. This was characterized by a marked inflammatory infiltrate, activation of NF-kappaB in both enterocytes and enteric nerves, and a threefold increase in neuronal galanin. Colonic fluid secretion, while increased, was approximately half that in GAL1R-/- mice as compared with their wild-type littermates. Overall, then, these findings strongly suggest that approximately half of the increase in colonic fluid secretion in DSS colitis is due to up-regulation of the Gal1R.
This article was published in Inflamm Bowel Dis
and referenced in Journal of Biotechnology & Biomaterials