Carbachol induces TGF-alpha expression and colonic epithelial cell proliferation in sensory-desensitised rats
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Signals for the expression of the peptide growth factors epidermal growth factor and transforming growth factor-α (TGFα) in the gastrointestinal mucosa are largely unknown. We have shown earlier that extrinsic afferents in the gastrointestinal tract induce TGFα expression in colonic mucosa via the deliberation of neurotransmitters substance P and calcitonin gene-related peptide. The aim of our present study was to determine the effects of carbachol on mucosal TGFα expression and epithelial cell proliferation in vivo.
Rats were divided in three groups. Group 1 was treated with vehicle only, group 2 received one single subcutaneous injection of 250 μg/kg of carbachol and animals in group 3 were sensory-desensitised prior to the injection of 250 μg/kg carbachol. TGFα expression and epithelial cell proliferation was evaluated by polymerase chain reaction, Western blot analysis and bromodeoxyuridine staining.
Carbachol induced a significant increase in mucosal epithelial cell proliferation and TGFα expression. Sensory desensitisation did neither abolish the increased TGFα expression nor the increase in epithelial cell proliferation.
Parasympathetic pathways are involved in the control of TGFα expression in gastrointestinal mucosa as well as in epithelial cell proliferation.