Persistent distention of colon damages interstitial cells of Cajal through Ca²⁺ -ERK-AP-1-miR-34c-SCF deregulation.

ABSTRACT: Gastrointestinal motility disorders (GMDs) are attributed to loss of interstitial cells of Cajal (ICC), whose survival and function are deeply dependent on the activation of KIT/SCF signalling. Based on the facts that gastrointestinal distention is common in GMD patients and SCF produced by smooth muscle cells (SMCs) is usually decreased before ICC loss, we considered a possible contribution of persistent gastrointestinal distention/stretch to SCF deficiency. In this study, chronic colonic distention mouse model, diabetic gastrointestinal paresis mouse model, cultured mouse colonic SMCs and colon specimens from Hirschsprung's disease patients were used. The results showed that SCF was clearly decreased in distent colon of mice and patients, and microRNA array and real-time PCR indicated a

SUBMITTER: Yang S 

PROVIDER: S-EPMC5571545 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature