{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T20:16:34Z","timestamp":1789848994016,"version":"4.0.1"},"posted":{"date-parts":[[2024,10,15]]},"group-title":"Bioengineering","reference-count":91,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T00:00:00Z","timestamp":1728950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background and Aims<\/jats:title>\n                  <jats:p>Bowel smooth muscle experiences mechanical stress constantly during normal function, and pathologic mechanical stressors in disease states. We tested the hypothesis that pathologic mechanical stress could alter transcription to induce smooth muscle phenotypic class switching.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Primary human intestinal smooth muscle cells (HISMCs), seeded on electrospun aligned poly-\u03b5-caprolactone nano-fibrous scaffolds, were subjected to pathologic, high frequency (1 Hz) uniaxial 3% cyclic stretch (loaded) or kept unloaded in culture for 6 hours. Total RNA sequencing, qRT-PCR, and quantitative immunohistochemistry defined loading-induced changes in gene expression. NicheNet predicted how differentially expressed genes might impact HISMCs and other bowel cells.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Loading induced differential expression of 4537 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 and on other cells in the bowel wall.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>HISMCs demonstrate remarkably rapid phenotypic plasticity in response to mechanical stress that may convert contractile HISMCs into proliferative, fibroblast-like cells or proinflammatory cells. These mechanical stress-induced changes in HISMC gene expression may be relevant for human bowel disease.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.10.12.617767","type":"posted-content","created":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T13:25:44Z","timestamp":1728998744000},"source":"Crossref","is-referenced-by-count":4,"title":["Rapid cyclic stretching induces a synthetic, proinflammatory phenotype in cultured human intestinal smooth muscle, with the potential to alter signaling to adjacent bowel cells"],"prefix":"10.64898","author":[{"given":"Sharon M.","family":"Wolfson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3439-6042","authenticated-orcid":false,"given":"Katherine","family":"Beigel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2131-807X","authenticated-orcid":false,"given":"Sierra E.","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8325-9346","authenticated-orcid":false,"given":"Brooke","family":"Deal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7359-9876","authenticated-orcid":false,"given":"Molly","family":"Weiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7679-2436","authenticated-orcid":false,"given":"Se-Hwan","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3302-4610","authenticated-orcid":false,"given":"Deanne","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2771-5076","authenticated-orcid":false,"given":"Su Chin","family":"Heo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3282-1765","authenticated-orcid":false,"given":"Robert O.","family":"Heuckeroth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5256-3820","authenticated-orcid":false,"given":"Sohaib K.","family":"Hashmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2024101811550500000_2024.10.12.617767v1.1","unstructured":"Yang Z , et al. PKC-delta and PKD activate MAPK signal pathway in mechano-transcription of colonic smooth muscle cells. Neurogastroenterol Motil. 2023;e14623."},{"key":"2024101811550500000_2024.10.12.617767v1.2","doi-asserted-by":"crossref","unstructured":"Geesala R , et al. Targeting Mechano-Transcription Process as Therapeutic Intervention in Gastrointestinal Disorders. Front Pharmacol. 2021;12:809350.","DOI":"10.3389\/fphar.2021.809350"},{"key":"2024101811550500000_2024.10.12.617767v1.3","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.01000"},{"key":"2024101811550500000_2024.10.12.617767v1.4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2012.01918.x"},{"key":"2024101811550500000_2024.10.12.617767v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-021-00561-y"},{"key":"2024101811550500000_2024.10.12.617767v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2009.02.011"},{"key":"2024101811550500000_2024.10.12.617767v1.7","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16367"},{"key":"2024101811550500000_2024.10.12.617767v1.8","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.110.221135"},{"key":"2024101811550500000_2024.10.12.617767v1.9","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00041.2003"},{"key":"2024101811550500000_2024.10.12.617767v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-27230-6"},{"key":"2024101811550500000_2024.10.12.617767v1.11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0106242"},{"key":"2024101811550500000_2024.10.12.617767v1.12","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1999.277.5.G1074"},{"key":"2024101811550500000_2024.10.12.617767v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2007.01.004"},{"key":"2024101811550500000_2024.10.12.617767v1.14","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.44.28860"},{"key":"2024101811550500000_2024.10.12.617767v1.15","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.107.1.307"},{"key":"2024101811550500000_2024.10.12.617767v1.16","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2010.0535"},{"key":"2024101811550500000_2024.10.12.617767v1.17","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.140604"},{"key":"2024101811550500000_2024.10.12.617767v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0439-x"},{"key":"2024101811550500000_2024.10.12.617767v1.19","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"2024101811550500000_2024.10.12.617767v1.20","doi-asserted-by":"crossref","unstructured":"Li B , Dewey CN . RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics. 2011;12:323.","DOI":"10.1186\/1471-2105-12-323"},{"key":"2024101811550500000_2024.10.12.617767v1.21","unstructured":"R Core Team (2024). R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria [Internet]. https:\/\/www.R-project.org\/."},{"key":"2024101811550500000_2024.10.12.617767v1.22","unstructured":"22. Posit team (2023). RStudio: Integrated Development Environment for R. Posit Software, PBC, Boston, MA [Internet]. http:\/\/www.posit.co\/."},{"key":"2024101811550500000_2024.10.12.617767v1.23","doi-asserted-by":"crossref","unstructured":"Langfelder P , Horvath S . WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008;9:559.","DOI":"10.1186\/1471-2105-9-559"},{"key":"2024101811550500000_2024.10.12.617767v1.24","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"2024101811550500000_2024.10.12.617767v1.25","unstructured":"Sergushichev A , et al. Fast gene set enrichment analysis. bioRxiv. 2019."},{"key":"2024101811550500000_2024.10.12.617767v1.26","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"2024101811550500000_2024.10.12.617767v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/J.CELS.2015.12.004"},{"key":"2024101811550500000_2024.10.12.617767v1.28","doi-asserted-by":"publisher","DOI":"10.1038\/ng1180"},{"key":"2024101811550500000_2024.10.12.617767v1.29","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1131"},{"key":"2024101811550500000_2024.10.12.617767v1.30","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0667-5"},{"key":"2024101811550500000_2024.10.12.617767v1.31","doi-asserted-by":"publisher","DOI":"10.1016\/J.CELL.2021.04.048"},{"key":"2024101811550500000_2024.10.12.617767v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.08.003"},{"key":"2024101811550500000_2024.10.12.617767v1.33","unstructured":"33. Breitwieser F, Gandrud C, Allaire J, Russell K, Bostock M (2017). sankeyD3: D3 JavaScript Sankey Graphs from R. R package version 0.3.2,commit fd50a74e29056e0d67d75b4d04de47afb2f932bc [Internet]. https:\/\/github.com\/fbreitwieser\/sankeyD3."},{"key":"2024101811550500000_2024.10.12.617767v1.34","first-page":"203","article-title":"Matrix stiffness determines the phenotype of vascular smooth muscle cell in vitro and in vivo: Role of DNA methyltransferase 1","volume":"155","year":"2017","journal-title":"Biomaterials"},{"key":"2024101811550500000_2024.10.12.617767v1.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2015.09.102"},{"key":"2024101811550500000_2024.10.12.617767v1.36","doi-asserted-by":"crossref","unstructured":"Agrawal A , et al. Smooth Muscle Cell Alignment and Phenotype Control by Melt Spun Polycaprolactone Fibers for Seeding of Tissue Engineered Blood Vessels. Int J Biomater. 2015;2015:434876.","DOI":"10.1155\/2015\/434876"},{"key":"2024101811550500000_2024.10.12.617767v1.37","doi-asserted-by":"publisher","DOI":"10.1039\/c1ib00061f"},{"key":"2024101811550500000_2024.10.12.617767v1.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2008.11.074"},{"key":"2024101811550500000_2024.10.12.617767v1.39","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.142339"},{"key":"2024101811550500000_2024.10.12.617767v1.40","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.113.000230"},{"key":"2024101811550500000_2024.10.12.617767v1.41","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.4.1633"},{"key":"2024101811550500000_2024.10.12.617767v1.42","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)00093-7"},{"key":"2024101811550500000_2024.10.12.617767v1.43","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.121.316600"},{"key":"2024101811550500000_2024.10.12.617767v1.44","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.106.2.403"},{"key":"2024101811550500000_2024.10.12.617767v1.45","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.026644"},{"key":"2024101811550500000_2024.10.12.617767v1.46","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24403"},{"key":"2024101811550500000_2024.10.12.617767v1.47","doi-asserted-by":"publisher","DOI":"10.1530\/JME-22-0178"},{"key":"2024101811550500000_2024.10.12.617767v1.48","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.151282"},{"key":"2024101811550500000_2024.10.12.617767v1.49","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00864.2006"},{"key":"2024101811550500000_2024.10.12.617767v1.50","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2023.03.229"},{"key":"2024101811550500000_2024.10.12.617767v1.51","doi-asserted-by":"publisher","DOI":"10.1038\/75556"},{"key":"2024101811550500000_2024.10.12.617767v1.52","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/iyad031"},{"key":"2024101811550500000_2024.10.12.617767v1.53","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23136917"},{"key":"2024101811550500000_2024.10.12.617767v1.54","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13757"},{"key":"2024101811550500000_2024.10.12.617767v1.55","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00379.2010"},{"key":"2024101811550500000_2024.10.12.617767v1.56","doi-asserted-by":"crossref","unstructured":"Luo Y , Zheng SG . Hall of Fame among Pro-inflammatory Cytokines: Interleukin-6 Gene and Its Transcriptional Regulation Mechanisms. Front Immunol. 2016;7:604.","DOI":"10.3389\/fimmu.2016.00604"},{"key":"2024101811550500000_2024.10.12.617767v1.57","doi-asserted-by":"publisher","DOI":"10.4331\/wjbc.v3.i3.41"},{"key":"2024101811550500000_2024.10.12.617767v1.58","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01311"},{"key":"2024101811550500000_2024.10.12.617767v1.59","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1890"},{"key":"2024101811550500000_2024.10.12.617767v1.60","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708137200"},{"key":"2024101811550500000_2024.10.12.617767v1.61","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202101817RR"},{"key":"2024101811550500000_2024.10.12.617767v1.62","doi-asserted-by":"publisher","DOI":"10.3390\/cells10092209"},{"key":"2024101811550500000_2024.10.12.617767v1.63","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.123.031121"},{"key":"2024101811550500000_2024.10.12.617767v1.64","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.320381"},{"key":"2024101811550500000_2024.10.12.617767v1.65","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00260.2016"},{"key":"2024101811550500000_2024.10.12.617767v1.66","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00429.2009"},{"key":"2024101811550500000_2024.10.12.617767v1.67","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M703914200"},{"key":"2024101811550500000_2024.10.12.617767v1.68","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvssci.2021.04.001"},{"key":"2024101811550500000_2024.10.12.617767v1.69","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.14462"},{"key":"2024101811550500000_2024.10.12.617767v1.70","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(83)80009-2"},{"key":"2024101811550500000_2024.10.12.617767v1.71","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2005.00718.x"},{"key":"2024101811550500000_2024.10.12.617767v1.72","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.055949"},{"key":"2024101811550500000_2024.10.12.617767v1.73","doi-asserted-by":"publisher","DOI":"10.1002\/2211-5463.12430"},{"key":"2024101811550500000_2024.10.12.617767v1.74","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00390.2014"},{"key":"2024101811550500000_2024.10.12.617767v1.75","doi-asserted-by":"publisher","DOI":"10.1002\/iub.298"},{"key":"2024101811550500000_2024.10.12.617767v1.76","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-74944-7"},{"key":"2024101811550500000_2024.10.12.617767v1.77","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvq076"},{"key":"2024101811550500000_2024.10.12.617767v1.78","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00066.2021"},{"key":"2024101811550500000_2024.10.12.617767v1.79","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705842105"},{"key":"2024101811550500000_2024.10.12.617767v1.80","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.08.041"},{"key":"2024101811550500000_2024.10.12.617767v1.81","doi-asserted-by":"crossref","unstructured":"Zhang M , et al. BMP-2 overexpression augments vascular smooth muscle cell motility by upregulating myosin Va via Erk signaling. Oxid Med Cell Longev. 2014;2014:294150.","DOI":"10.1155\/2014\/294150"},{"key":"2024101811550500000_2024.10.12.617767v1.82","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2007.11.031"},{"key":"2024101811550500000_2024.10.12.617767v1.83","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2018.12.001"},{"key":"2024101811550500000_2024.10.12.617767v1.84","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.03.011"},{"key":"2024101811550500000_2024.10.12.617767v1.85","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2016.105"},{"key":"2024101811550500000_2024.10.12.617767v1.86","doi-asserted-by":"publisher","DOI":"10.4251\/wjgo.v14.i5.973"},{"key":"2024101811550500000_2024.10.12.617767v1.87","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00308"},{"key":"2024101811550500000_2024.10.12.617767v1.88","doi-asserted-by":"publisher","DOI":"10.32604\/biocell.2023.026545"},{"key":"2024101811550500000_2024.10.12.617767v1.89","doi-asserted-by":"publisher","DOI":"10.1113\/JP284745"},{"key":"2024101811550500000_2024.10.12.617767v1.90","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021317-121515"},{"key":"2024101811550500000_2024.10.12.617767v1.91","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastha.2022.12.004"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.10.12.617767","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T07:16:07Z","timestamp":1768461367000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.10.12.617767"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,15]]},"references-count":91,"URL":"https:\/\/doi.org\/10.1101\/2024.10.12.617767","relation":{},"subject":[],"published":{"date-parts":[[2024,10,15]]},"subtype":"preprint"}}