Z Gastroenterol 2009; 47 - P1_13
DOI: 10.1055/s-0029-1191767

Elevated concentrations of 15-deoxy-Δ12,14-Prostaglandin J2 in chronic liver disease propose therapeutic trials with PPARgamma inducing drugs

OA Gressner 1, C Gao 2, K Rehbein 1, B Lahme 1, T Müller 3, T Berg 3, AM Gressner 1
  • 1Institut für Klinische Chemie und Pathobiochemie, Universitätsklinikum der RWTH Aachen
  • 2Department of Laboratory Medicine, Eastern Hepatobiliary Hospital (EHBH), Second Military Medical University
  • 3Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie; Charité – Campus Virchow Klinikum, Berlin

Aims: Current knowledge attributes connective tissue growth factor (CTGF/CCN2) a crucial role in hepatic fibrogenesis and–very likely–carcinogenesis. Hepatocytes are the major cellular source of CTGF in the liver in which CTGF is sensitively upregulated by TGF-β. In another abstract, we demonstrate that the methylxanthine derivate caffeine leads to an upregulation of PPARγ expression in hepatocytes, thus sensitizing these cells to the well known inhibitory effect of 15-deoxy-Δ12,14-prostaglandin J2 (15-d-PGJ2) on CTGF expression. However, upregulation of the receptor alone is not sufficient per se, its physiological ligand 15-d-PGJ2 is required for exerting its inhibitory effect on TGF-β target genes such as CTGF.

Aim and Methods: This study compares serum concentrations of 15-d-PGJ2 in Caucasian patients with fibrotic liver diseases (n=289), Caucasian controls (n=136) and Caucasian non-liver disease sick (n=307), as well as of Chinese patients with hepatocellular carcinoma (n=43) and Chinese healthy controls (n=63) in order to characterize their suitability for therapeutic approaches with PPARγ inducing (i.e. CTGF inhibitory) drugs such as caffeine.

Results: Presented data show that Caucasian patients with ongoing hepatic fibrogenesis (mean 6.2±5.9µg/L) display impressingly higher serum concentrations of 15-d-PGJ2 than healthy probands (mean 2.3±1.0) and Caucasian patients with non-liver disease (mean 2.7±1.4µg/L). Similar results are found in Chinese patients with fully developed HCC (mean 1.3±0.7µg/L) compared to Chinese healthy controls (mean 0.4±0.2µg/L).

Conclusion: In conclusion, our data thus propose an increased suitability of these patient groups for therapeutic approaches with drugs inducing PPARγ expression, such as methylxanthine derivates.