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Early response to cyclic stretch in human intestinal smooth muscle activates transition to a synthetic, proinflammatory phenotype hypothesized to affect gene expression in nearby cells in the bowel wall

ABSTRACT: Background and Aims: Bowel smooth muscle experience mechanical stress constantly during normal function, and unusual mechanical stressors in various disease settings. Here, we test the hypothesis that pathologic mechanical stress could alter transcription to induce smooth muscle phenotypic class switching. Methods: Primary human intestinal smooth muscle cells (HISMCs), seeded on electrospun aligned poly-ε-caprolactone nano-fibrous scaffolds, were subjected to uniaxial 3% cyclic stretch at 1 Hz (loaded) or kept unloaded in culture for 6 hours. Bulk total RNA sequencing, RT-qPCR, and quantitative immunohistochemistry defined loading-induced changes in gene expression. NicheNet predicted how differentially expressed genes might impact HISMCs and other bowel cells. Results: Loading induced differential expression of 2500 genes in HISMCs. Loaded HISMCs had a less contractile phenotype, with increased expression of synthetic SMC genes, proinflammatory cytokines, and altered expression of axon guidance molecules, growth factors and morphogens. Many differentially expressed genes encode secreted ligands that could act cell-autonomously on smooth muscle, but also on other cells in the bowel wall. Discussion: HISMCs demonstrate remarkably rapid phenotypic plasticity in response to mechanical stress that may convert contractile HISMC into proliferative fibroblast-like cells or proinflammatory cells. These mechanical stress-induced changes in HISMC gene expression may be relevant for human bowel disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE264225 | GEO | 2024/12/04

REPOSITORIES: GEO

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Early response to cyclic stretch in human intestinal smooth muscle activates transition to a synthetic, proinflammatory phenotype hypothesized to affect gene expression in nearby cells in the bowel wall

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