title: Decreased SCF/c-kit signaling pathway contributes to loss of interstitial cells of Cajal in gallstone disease.
abstract: Cholecystolithiasis is a common disease, and gallbladder dysmotility is considered as a pivotal pathogenesis. Interstitial cells of Cajal (ICCs) serve as pacemakers and mediators of neuromuscular transmission for gastrointestinal motility. Reduction of ICCs has been reported in gallstone diseases. However, there are no reasonable mechanisms for the cholecystolithiasis-associated loss of ICCs in humans. Stem cell factor (SCF) and its ligand c-kit are essential for normal development and survival of ICCs. To date, little is known about the SCF/c-kit signaling pathway in gallstone diseases. The purpose of this study was to investigate the role of the SCF/c-kit signaling pathway in the loss of ICCs in cholecystolithiasis. Data from 18 patients with gallstones and 14 individuals without gallstones were compared. The gallbladder contractility was assessed by measuring the gallbladder ejection fraction (GEF) ultrasonographically. Tissues samples were obtained during surgery, changes of ICC quantities were analyzed by immunohistochemistry, and the mRNA and protein expression of SCF and c-kit were detected by Real-Time PCR and Western-blot analysis. Compared with the controls, the GEF was significantly reduced in the gallstone group, and decreased number of ICCs was present obviously in the gallstone group. Furthermore, the mRNA and protein expression of SCF and c-kit were significantly attenuated in the gallstone group. These data indicate that gallbladder motility may be affected by reduction of ICCs in gallstone disease. Additionally, the decreased of SCF/c-kit signaling pathway play an important role in the loss of ICCs.
authors.affiliation: Department of General Surgery, Institute for Minimally Invasive Surgery, Zhongda Hospital, College of Medicine & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University Nanjing 210009, Jiangsu, China.
authors.forename: Yu-Yan
authors.initials: YY
authors.lastname: Tan
authors.affiliation: Department of General Surgery, Institute for Minimally Invasive Surgery, Zhongda Hospital, College of Medicine & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University Nanjing 210009, Jiangsu, China.
authors.forename: Zhen-Ling
authors.initials: ZL
authors.lastname: Ji
authors.affiliation: Department of General Surgery, Institute for Minimally Invasive Surgery, Zhongda Hospital, College of Medicine & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University Nanjing 210009, Jiangsu, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University Changsha, Hunan 410000, China.
authors.forename: Jia-Rui
authors.initials: JR
authors.lastname: Jiang
authors.affiliation: Department of General Surgery, Institute for Minimally Invasive Surgery, Zhongda Hospital, College of Medicine & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University Nanjing 210009, Jiangsu, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Institute for Minimally Invasive Surgery, Zhongda Hospital, College of Medicine & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University Nanjing 210009, Jiangsu, China.
authors.forename: Jing-Min
authors.initials: JM
authors.lastname: Wang
keywords: Gallstone disease; c-kit; gallbladder motility; interstitial cells of Cajal; stem cell factor