Exogenous stem cell factor improves interstitial cells of Cajal restoration after blockade of c-kit signaling pathway. Scand J Gastroenterol 2010 Aug;45(7-8):844-51
Date
04/10/2010Pubmed ID
20377480DOI
10.3109/00365521003782371Scopus ID
2-s2.0-77955693527 (requires institutional sign-in at Scopus site) 28 CitationsAbstract
OBJECTIVE: Interstitial cells of Cajal (ICC) have been endowed with considerable intrinsic plasticity. Blockade of the c-kit signaling pathway results in the shift of ICC towards a smooth muscle-like phenotype. Little is known about stem cell factor (SCF), the ligand of c-kit, and the role it plays in the process of restoration. The aim of this study was to determine whether exogenous SCF can promote ICC replenishment following the blockade of c-kit signaling.
MATERIAL AND METHODS: Neutralizing anti-c-kit monoclonal antibody (ACK2) was administered to mice for 8 days after birth. Jejunal muscle strips were cultured up to 7 days. Electrical rhythmic changes were monitored and ICC were examined by immunohistochemistry. Expression of c-kit mRNA was detected by reverse transcriptase-polymerase chain reaction, and expression of Kit protein was detected by Western blot.
RESULTS: When c-kit receptors were blocked, ICC nearly disappeared from the jejunum accompanied by the loss of electrical slow waves. By day 7, after in vitro culture with SCF (100 ng/ml), the amplitude of muscle strip slow waves was restored to 0.19 +/- 0.07 mV (p < 0.05), whereas the frequency recovered to 13.7 +/- 3.32/min (p < 0.01). Furthermore, labeling for c-kit(+) cells in the myenteric plexus increased and c-kit mRNA and protein expression were up-regulated compared to that of non-treatment with SCF.
CONCLUSIONS: The c-kit signaling pathway, activated by SCF, is the critical pathway associated with the control of ICC survival and proliferation. The restoration of ICC number and jejunal electrical rhythm, resulting from blockade of the c-kit signaling pathway, could be facilitated by local SCF administration.
Author List
Tong W, Jia H, Zhang L, Li C, Ridolfi TJ, Liu BAuthor
Timothy J. Ridolfi MD, MS, FACS Associate Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCell Differentiation
Gastrointestinal Motility
Interstitial Cells of Cajal
Mice
Mice, Inbred BALB C
Proto-Oncogene Proteins c-kit
Signal Transduction
Stem Cell Factor