平滑肌
克罗恩病
胃肠病学
医学
增生
内科学
疾病
粘膜肌层
病理
作者
Ren Mao,Geneviève Doyon,Satya Kurada,Ilyssa O. Gordon,Shuai Zhao,Dina Dejanovic,Gail West,Julie H. Rennison,David R. Van Wagoner,Claudio Fiocchi,Florian Rieder
标识
DOI:10.1016/s0016-5085(18)30866-7
摘要
time point in the no DSS mice did not lead to any signs of inflammation or fibrosis.Among all bacterial ligands HIMF selectively responded to flagellin (in form of S. typhimurium coculture or a synthetic peptide) with FN or Col1 protein production.Flagellin-induced FN secretion was dependent on MyD88 and was not associated with changes in the levels of a-SMA.mRNA levels of Col I and FN remained unchanged.Polysome profiling revealed higher proportions of FN and Col1 mRNA in the actively translated fractions of flagellin exposed HIMF.Preliminary results suggest that all bacterial ligands induced phosphorylation of AKT and mTOR.Only flagellin, but not activation of TLR4 or NOD1, dephosphorylated eIF2alpha and phosphorylated 4EBP, suggesting that the selectivity of flagellin-dependent ECM secretion, is translationally regulated.Conclusions: Selective deletion of MyD88 signaling in a-SMA positive cells prior to but not after induction of experimental fibrosis ameliorates ECM deposition, but not clinical signs of colitis or histopathologic signs of inflammation.HIMF selectively upregulated ECM secretion by flagellin via MyD88 and post-transcriptional regulation.This may represent a novel and targetable link between the microbiota and intestinal fibrosis.
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