The expression of hepatic carboxypeptidase E is decreased in patients with cholesterol gallstone

Saudi J Gastroenterol. Jul-Aug 2015;21(4):226-31. doi: 10.4103/1319-3767.161640.

Abstract

Background/aims: Decreased carboxypeptidase E (CPE) expression is associated with numerous pathophysiological conditions. This study aimed to investigate the potential function of hepatic CPE in cholesterol gallstone formation.

Patients and methods: Patients with cholesterol gallstone (CGS group) and patients without cholesterol gallstones (non-CGS group) were enrolled. The serum total cholesterol, triglyceride, and biliary composition were analyzed. Eight liver samples from two patients without CGS and six patients with CGS were subjected to cDNA microarray analysis. Hepatic CPE expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemical analysis. Plasma CCK level was measured by ELISA.

Results: cDNA microarray identified CPE as a gene downregulated in the CGS group. RT-PCR showed that CPE mRNA level was lower in CGS group than in control (P < 0.05, t-test). Moreover, Western blot and immunohistochemistry analysis showed that CPE protein level was significantly lower in CGS group than in the control group. In addition, plasma CCK level was lower in CGS group than in the control group. A positive correlation was found between serum CCK level and hepatic CPE mRNA level (r2 = 0.713, P = 0.003).

Conclusions: Down-expression of liver CPE may reduce the secretion of serum CCK and contribute to the formation of cholesterol gallstone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carboxypeptidase H / genetics
  • Carboxypeptidase H / metabolism*
  • Case-Control Studies
  • Cholecystokinin / blood
  • Cholesterol
  • Female
  • Gallstones / chemistry
  • Gallstones / metabolism*
  • Humans
  • Liver / enzymology*
  • Male
  • Middle Aged
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction

Substances

  • RNA, Messenger
  • Cholecystokinin
  • Cholesterol
  • Carboxypeptidase H