Alteration in transforming growth factor-β receptor expression in gallbladder disease: implications of chronic cholelithiasis and chronic Salmonella typhi infection

Gallbladder cancer prevalence is ever increasing with <em>Salmonella typhi</em> chronic infection being one of the predisposing factors. Altered ratios or expression of transforming growth factor-β (TGF-β) receptors and changes in its function are associated with loss in anti-proliferative effects of TGF-β and cancer progression. Using reverse transcriptase polymerase chain reaction we monitor any changes in TGF-β receptor gene expression. We simultaneously screen for <em>S. typhi</em> within the samples. From 73 patients undergoing cholecystectomy 39-50% had significant expression (P&lt;0.05) of TGF-β receptor (TβR)- I and TβR-II during chronic cholelithiasis as compared to the remaining 19-23% with acute chronic cholelithiasis. There was no significant increase in TβR-III receptor expression. Patient’s positive for <em>S. typhi</em> (7/73) did not show any significant changes in expression of these receptors, thus indicating no direct relation in regulating the host TGFβ-signaling pathway. Further analysis on expression of downstream Smad components revealed that patients with up-regulated TGFβ receptor expression show &gt;2-fold increase in the RSmads and Co-Smads with a &gt;2-fold decrease in I-Smads. Thus gain of TβR-I and II expression in epithelial cells of the gallbladder was associated with chronic inflammatory stages of the gallbladder disease.