Digestive Diseases and Sciences

, Volume 54, Issue 8, pp 1651–1655 | Cite as

Expression of C-kit Messenger Ribonucleic Acid and C-kit Protein in the Gallbladders in Guinea Pigs of High Cholesterol Diet

  • Wang-Ming Hu
  • He-Sheng Luo
  • Xiang-Wu Ding
  • Ling Wang
Original Article


The c-kit protooncogene receptor and its ligand-stem cell factor regulating the proliferation and survival of interstitial cells of Cajal (ICCs) have been described. The aim of this study was to determine the expression of c-kit mRNA and c-kit protein in the gallbladders in guinea pigs of high cholesterol diet (HCD). The gallbladder samples from 16 guinea pigs of HCD and from 16 guinea pigs of standard diet (StD) were used for this study. Expression of c-kit mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR), and expression of c-kit protein was detected by Western blot analysis. Serum total cholesterol (TC) (39 ± 6 vs. 109 ± 20 mg/dl), low density lipoprotein (LDL) cholesterol (24 ± 4 vs. 71 ± 10 mg/dl), high density lipoprotein (HDL) cholesterol (2.4 ± 0.4 vs. 7.0 ± 1.6 mg/dl), and triglyceride (TG) (58 ± 8 vs. 118 ± 23 mg/dl) concentrations were significantly higher in the HCD group than in the StD group of guinea pigs (P < 0.001, respectively). Decreased expression of c-kit mRNA was demonstrated in the HCD group compared with the StD group. The ratio of c-kit mRNA and GAPDH was 0.56 ± 0.09 in controls and 0.50 ± 0.07 in the HCD group (P = 0.033). C-kit protein expression significantly declined in the HCD group. The mean value of optical density was 129 ± 25 in the StD group and 103 ± 19 in the HCD group (P = 0.0009). The data indicate that the expression of c-kit mRNA and c-kit protein significantly decreased in the gallbladders in guinea pigs of HCD.


Gallbladder C-kit Interstitial cells of Cajal 


  1. 1.
    Ward SM, Sanders KM. Physiology and pathophysiology of the interstitial cell of Cajal: from bench to bedside. I. Functional development and plasticity of interstitial cells of Cajal networks. Am J Physiol Gastrointest Liver Physiol. 2001;281:G602–G611.PubMedGoogle Scholar
  2. 2.
    Sun X, Yu B, Xu L, et al. Interstitial cells of Cajal in the murine gallbladder. Scand J Gastroenterol. 2006;41:1218–1226. doi:10.1080/00365520600708800.PubMedCrossRefGoogle Scholar
  3. 3.
    Lavoie B, Balemba OB, Nelson MT, Ward SM, Mawe GM. Morphological and physiological evidence for interstitial cell of Cajal-like cells in the guinea pig gallbladder. J Physiol. 2007;579.2:487–501.Google Scholar
  4. 4.
    Xu QW, Shaffer EA. The potential site of impaired gallbladder contractility in an animal model of cholesterol gallstone disease. Gastroenterology. 1996;110:251–257.PubMedCrossRefGoogle Scholar
  5. 5.
    Jennings LJ, Xu QW, Firth TA, Nelson MT, Mawe GM. Cholesterol inhibits spontaneous action potentials and calcium currents in guinea pig gallbladder smooth muscle. Am J Physiol. 1999;277(5 Pt 1):G1017–G1026.PubMedGoogle Scholar
  6. 6.
    Sanders KM, Ordog T, Koh SD, Torihashi S, Ward SM. Development and plasticity of interstitial cells of Cajal. Neurogastroenterol Motil. 1999;11:311–338. doi:10.1046/j.1365-2982.1999.00164.x.PubMedCrossRefGoogle Scholar
  7. 7.
    Wu JJ, Rothman TP, Gershon MD. Development of the interstitial cell of Cajal: origin, kit dependence and neuronal and nonneuronal sources of kit ligand. J Neurosci Res. 2000;59:384–401. doi:10.1002/(SICI)1097-4547(20000201)59:3<384::AID-JNR13>3.0.CO;2-4.PubMedCrossRefGoogle Scholar
  8. 8.
    Torihashi S, Nishi K, Tokutomi Y, Nishi T, Ward S, Sanders KM. Blockade of kit signaling induces transdifferentiation of interstitial cells of Cajal to a smooth muscle phenotype. Gastroenterology. 1999;117:140–148. doi:10.1016/S0016-5085(99)70560-3.PubMedCrossRefGoogle Scholar
  9. 9.
    Daniel EE, Bodie G, Mannarino M, Boddy G, Cho WJ. Changes in membrane cholesterol affect caveolin-1 localization and ICC-pacing in mouse jejunum. Am J Physiol Gastrointest Liver Physiol. 2004;287:G202–G210. doi:10.1152/ajpgi.00356.2003.PubMedCrossRefGoogle Scholar
  10. 10.
    Hirota S, Isozaki K, Nishida T, Kitamura Y. Effects of loss-of-function and gain-of-function mutations of c-kit on the gastrointestinal tract. J Gastroenterol. 2000;35(suppl 12):75–79. doi:10.1007/PL00009983.PubMedGoogle Scholar
  11. 11.
    Kitamura Y, Hirota S, Nishida T. A loss-of-function mutation of c-kit results in depletion of mast cells and interstitial cells of Cajal, while its gain-of- function mutation results in their oncogenesis. Mutat Res. 2001;477:165–171. doi:10.1016/S0027-5107(01)00117-8.PubMedGoogle Scholar
  12. 12.
    Lecoin L, Gabella G, Le Douarin N. Origin of the c-kit-positive interstitial cells in the avian bowel. Development. 1996;122:725–733.PubMedGoogle Scholar
  13. 13.
    Rich A, Miller SM, Gibbons SJ, Malysz J, Szurszewski JH, Farrugia G. Local presentation of steel factor increases expression of c-kit immunoreactive interstitial cells of Cajal in culture. Am J Physiol Gastrointest Liver Physiol. 2003;284:G313–G320.PubMedGoogle Scholar
  14. 14.
    Maeda H, Yamagata A, Nishikawa S, Yoshinaga K, Kobayashi S, Nishi K. Requirement of c-kit for development of intestinal pacemaker system. Development. 1992;116:369–375.PubMedGoogle Scholar
  15. 15.
    Torihashi S, Ward SM, Nishikawa S, Nishi K, Kobayashi S, Sanders KM. C-kit-dependent development of interstitial cells and electrical activity in the murine gastrointestinal tract. Cell Tissue Res. 1995;280:97–111.PubMedGoogle Scholar
  16. 16.
    Mendoza-Marin M, Hoang MP, Albores-Saavedra J. Malignant stromal tumor of the gallbladder with interstitial cells of Cajal phenotype. Arch Pathol Lab Med. 2002;126:481–483.PubMedGoogle Scholar
  17. 17.
    Park JK, Choi SH, Lee S, Min KO, Yun SS, Jeon HM. Malignant gastrointestinal stromal tumor of the gallbladder. J Korean Med Sci. 2004;19:763–767.PubMedCrossRefGoogle Scholar
  18. 18.
    Furihata M, Fujimori T, Imura J, et al. Malignant stromal tumor, so called ‘gastrointestinal stromal tumor’, with rhabdomyomatous differentiation occurring in the gallbladder. Pathol Res Pract. 2005;201:609–613. doi:10.1016/j.prp.2005.04.011.PubMedCrossRefGoogle Scholar
  19. 19.
    Popescu LM, Hinescu ME, Lonescu N, Ciontea SM, Cretoiu D, Ardelean C. Interstitial cells of Cajal in pancreas. J Cell Mol Med. 2005;9:169–190. doi:10.1111/j.1582-4934.2005.tb00347.x.PubMedCrossRefGoogle Scholar
  20. 20.
    Shimojima N, Nakaki T, Morikawa Y, Hoshino K, Kitajima M. Imatinib blocks spontaneous mechanical activities in the adult mouse small intestine: possible inhibition of c-kit signaling. Pharmacology. 2005;74:95–99. doi:10.1159/000084021.PubMedCrossRefGoogle Scholar
  21. 21.
    Popescu LM, Vidulescu C, Curici A, et al. Imatinib inhibits spontaneous rhythmic contractions of human uterus and intestine. Eur J Pharmacol. 2006;546:177–181. doi:10.1016/j.ejphar.2006.06.068.PubMedCrossRefGoogle Scholar
  22. 22.
    Kubota Y, Biers SM, Kohri K, Brading AF. Effects of imatinib mesylate (Glivec) as a c-kit tyrosine kinase inhibitor in the guinea-pig urinary bladder. Neurourol Urodyn. 2006;25:205–210. doi:10.1002/nau.20085.PubMedCrossRefGoogle Scholar
  23. 23.
    Biers SM, Reynard JM, Doore T, Brading AF. The functional effects of a c-kit tyrosine inhibitor on guinea-pig and human detrusor. BJU Int. 2006;97:612–616. doi:10.1111/j.1464-410X.2005.05988.x.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Wang-Ming Hu
    • 1
    • 2
  • He-Sheng Luo
    • 1
  • Xiang-Wu Ding
    • 1
  • Ling Wang
    • 1
  1. 1.Department of Gastroenterology, Renmin HospitalWuhan UniversityWuhan CityPeople’s Republic of China
  2. 2.Department of GastroenterologyGeneral HospitalHubeiPeople’s Republic of China

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