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Based on the facts that gastrointestinal distention is common in <jats:styled-content style=\"fixed-case\">GMD<\/jats:styled-content> patients and <jats:styled-content style=\"fixed-case\">SCF<\/jats:styled-content> produced by smooth muscle cells (<jats:styled-content style=\"fixed-case\">SMC<\/jats:styled-content>s) is usually decreased before <jats:styled-content style=\"fixed-case\">ICC<\/jats:styled-content> loss, we considered a possible contribution of persistent gastrointestinal distention\/stretch to <jats:styled-content style=\"fixed-case\">SCF<\/jats:styled-content> deficiency. In this study, chronic colonic distention mouse model, diabetic gastrointestinal paresis mouse model, cultured mouse colonic <jats:styled-content style=\"fixed-case\">SMC<\/jats:styled-content>s and colon specimens from Hirschsprung's disease patients were used. The results showed that <jats:styled-content style=\"fixed-case\">SCF<\/jats:styled-content> was clearly decreased in distent colon of mice and patients, and micro<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> array and real\u2010time <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> indicated a concomitant increase of <jats:italic>miR\u201034c<\/jats:italic> in distent colon. A negative regulation of <jats:italic>miR\u201034c<\/jats:italic> on <jats:styled-content style=\"fixed-case\">SCF<\/jats:styled-content> expression was confirmed by luciferase reporter assays together with knock\u2010down and overexpression of <jats:italic>miR\u201034c<\/jats:italic> in cultured colonic <jats:styled-content style=\"fixed-case\">SMC<\/jats:styled-content>s. Using <jats:styled-content style=\"fixed-case\">EMSA<\/jats:styled-content> and Ch<jats:styled-content style=\"fixed-case\">IP<\/jats:styled-content> assays, we further consolidated that in response to persistent stretch, the transcription factor <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20101\/c\u2010Jun was highly activated in colonic <jats:styled-content style=\"fixed-case\">SMC<\/jats:styled-content>s and significantly promoted <jats:italic>miR\u201034c<\/jats:italic> transcription by binding to <jats:italic>miR\u201034c<\/jats:italic> promoter. Knock\u2010down or overexpression of <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20101\/c\u2010Jun in cultured colonic <jats:styled-content style=\"fixed-case\">SMC<\/jats:styled-content>s leads to down\u2010 or up\u2010regulation of <jats:italic>miR\u201034c<\/jats:italic>, respectively. In addition, the activation of <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20101\/c\u2010Jun was through <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>1\/2 signalling provoked by Ca<jats:sup>2+<\/jats:sup> overload in colonic <jats:styled-content style=\"fixed-case\">SMC<\/jats:styled-content>s that were subject to persistent stretch. In conclusion, our data demonstrated that persistent distention\/stretch on colonic <jats:styled-content style=\"fixed-case\">SMC<\/jats:styled-content>s could suppress <jats:styled-content style=\"fixed-case\">SCF<\/jats:styled-content> production probably through Ca<jats:sup>2+<\/jats:sup>\u2010<jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20101\u2010<jats:italic>miR\u201034c<\/jats:italic> deregulation, resulting in <jats:styled-content style=\"fixed-case\">ICC<\/jats:styled-content> loss or impairment and <jats:styled-content style=\"fixed-case\">GMD<\/jats:styled-content> progress.<\/jats:p>","DOI":"10.1111\/jcmm.13108","type":"journal-article","created":{"date-parts":[[2017,6,5]],"date-time":"2017-06-05T04:27:04Z","timestamp":1496636824000},"page":"1881-1892","source":"Crossref","is-referenced-by-count":7,"title":["Persistent distention of colon damages interstitial cells of Cajal through Ca<sup>2+<\/sup>\u2010<scp>ERK<\/scp>\u2010<scp>AP<\/scp>\u20101\u2010<i>miR\u201034c<\/i>\u2010<scp>SCF<\/scp> deregulation"],"prefix":"10.1111","volume":"21","author":[{"given":"Shu","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology School of Basic Medical Sciences Capital Medical University Beijing China"},{"name":"Beijing Key Laboratory of Cancer Invasion and Metastasis Research Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology School of Basic Medical Sciences Capital Medical University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dandan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology School of Basic Medical Sciences Capital Medical University Beijing China"},{"name":"Beijing Key Laboratory of Cancer 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