Differential expression and localization of IGF-I and IGF binding proteinsin inflamed rat colon

Recent studies indicate increased insulin-like growth factor I (IGF-I) expr ession and altered expression of IGF binding proteins (IGFBP) in the bowel during experimental colitis. This study analyzes the cellular sites of alte red IGF-I and IGFBP-expression in large bowel of rats with experimental col itis. Colitis was induced by colonic instillation of 2, 4, 6-trinitrobenzen esulfonic (TNB) acid in ethanol. Animals were sacrificed at 7 days after in duction of colitis. Cryostat sections of colon from TNB-treated and control rats were hybridized with S-35-labeled antisense probes for IGF-I, IGFBP-3 , IGFBP-4 and IGFBP-5. IGF-I mRNA was up-regulated in lamina propria cells, submucosa and smooth muscle of inflamed colon. IGFBP3 mRNA was localized t o lamina propria and was down-regulated in inflamed colon. IGFBP-4 and IGFB P-5 mRNAs were both upregulated in inflamed colon. IGFBP-4 mRNA was increas ed in lamina propria, submucosa and smooth muscle, whereas IGFBP-5 mRNA was increased in smooth muscle. Increased IGF-I expression in mesenchymal laye rs of colon during experimental colitis supports the hypothesis that IGF-X contributes to hyperplasia and fibrosis in response to inflammation. Altere d expression of IGFBP-3, IGFBP-4 and IGFBP-5 in specific bowel layers durin g colitis suggests that they play a role in modulating IGF-I action.