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

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-β1 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-β1. 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: α-smooth muscle actin, γ-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 fi...
Source: Am J Physiol Gastroi... - Category: Gastroenterology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research