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• W2092302523 endingPage "201" @default.
• W2092302523 startingPage "193" @default.
• W2092302523 abstract "Stricture formation occurs in ≈30% of patients with Crohn's disease (CD) and is a significant cause of morbidity. Strictures are characterized by intestinal smooth muscle cell hyperplasia, smooth muscle cell hypertrophy, and fibrosis due to excess net extracellular matrix production, including collagen. Transforming growth factor-β1 (TGF-β1) has profibrotic effects in many tissues due to its ability to regulate collagen expression and extracellular matrix dynamics. We previously showed that both insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) and TGF-β1 are expressed by normal human intestinal smooth muscle cells, bind to, and activate TGF-βRII/I receptors in these cells.Smooth muscle cells isolated from the muscularis propria of patients were used to prepare RNA, protein lysates, or placed into primary culture. IGFBP-3, TGF-β1, and collagen IαI expression was measured with quantitative reverse-transcription polymerase chain reaction (RT-PCR) and protein levels by enzyme-linked immunosorbent assay (ELISA) or immunoblot.Expression and production of IGFBP-3, TGF-β1, and collagen IαI were significantly increased specifically in smooth muscle cells isolated from regions of strictured intestine in CD compared to nonstrictured histologically normal resection margin. IGFBP-3 and TGF-β1 regulated collagen IαI expression and production via a TGF-βRII/I-dependent and Smad2/3-dependent mechanism. Upregulated (excess) collagen IαI expression and production in smooth muscle cells of strictures and basal collagen IαI in smooth muscle cells of normal margin were inhibited by immunoneutralization of IGFBP-3 or TGF-β1.The findings indicate that upregulated endogenous IGFBP-3 and TGF-β1 expression regulates excess collagen IαI production and contributes to fibrosis and stricture formation in CD." @default.
• W2092302523 created "2016-06-24" @default.
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• W2092302523 date "2011-01-01" @default.
• W2092302523 modified "2023-10-14" @default.
• W2092302523 title "Endogenous IGFBP-3 regulates excess collagen expression in intestinal smooth muscle cells of Crohnʼs disease strictures" @default.
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• W2092302523 doi "https://doi.org/10.1002/ibd.21351" @default.
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