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Old 10-03-2015, 09:20 AM
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rss Mechano Growth Factor - Increased IGF-IEc Expression and Mechano-Growth Factor Produc

Related Articles Increased IGF-IEc Expression and Mechano-Growth Factor Production in Intestinal Muscle of Fibrostenotic Crohn's Disease and Smooth Muscle Hypertrophy.

Am J Physiol Gastrointest Liver Physiol. 2015 Oct 1;:ajpgi.00414.2014

Authors: Li C, Vu K, Hazelgrove K, Kuemmerle JF

Abstract
The igf1 gene is alternatively spliced as IGF-IEa and IGF-IEc variants in humans. In fibrostenotic Crohn's disease, the fibrogenic cytokine TGF-?1 induces IGF-IEa expression, IGF-I production in intestinal smooth muscle and results in muscle hyperplasia and collagen I production that contribute to stricture formation. MGF derived from IGF-IEc induces skeletal and cardiac muscle hypertrophy following stress. We hypothesized that increased IGF-IEc expression and MGF production mediated smooth muscle hypertrophy also characteristic of fibrostenotic Crohn's disease. IGF-IEc transcripts and MGF protein were increased in muscle cells isolated from fibrostenotic intestine under regulation by endogenous TGF-?1. Erk5 and MEF-2C were phosphorylated in vivo in fibrostenotic muscle; both were phosphorylated and co-localized to nucleus in response to synthetic MGF in vitro. Smooth muscle-specific protein expression: ?-smooth muscle actin, ?-smooth muscle actin, desmin, and smoothelin was increased in affected intestine. Erk5 inhibition or MEF2C siRNA blocked smooth muscle-specific gene expression and hypertrophy induced by synthetic MGF. Conditioned media of cultured fibrostenotic muscle induced muscle hypertrophy that was inhibited by immunoneutralization of endogenous MGF or pro-IGF-IEc. The results indicate that TGF-?1-dependent IGF-IEc expression and MGF production in patients with fibrostenotic Crohn's disease regulates smooth muscle cell hypertrophy a critical factor that contributes to intestinal stricture formation.


PMID: 26428636 [PubMed - as supplied by publisher]



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