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.