Research article summary (published 30 Aug 2009):

Less Smad2 is good for you! A scientific update on coffee's liver benefits.

Full Abstract

Scientists at the National Institutes of Health have reported that increased coffee consumption is associated with a slower progression of fibrogenesis in patients with chronic and particularly alcoholic liver disease and a reduced incidence of heptocellular carcinoma. However, a causal mechanistic explanation was pending. New results indicate that the methylxanthine caffeine--a major component of coffee and the most widely consumed pharmacologically active substance in the world--might be responsible for this phenomenon, because it inhibits the synthesis of connective tissue growth factor (CTGF/CCN2) in liver parenchymal and nonparenchymal cells, primarily by inducing degradation of Smad2 (and to a much lesser extent Smad3) and thus impairment of transforming growth factor beta (TGF-beta) signaling. CTGF and TGF-beta play crucial roles in the fibrotic remodeling of various organs, and, ultimately, carcinogenesis. This article summarizes the clinical-epidemiological observations as well as the pathophysiological background and provides suggestions for the therapeutic use of (methyl)xanthine derivatives in the management of fibro-/carcinogenic (liver) diseases.

Author information

Author/s: Gressner, Olav A (OA);

Affiliation: Institute of Clinical Chemistry and Pathobiochemistry, Central Laboratory, RWTH University Hospital, Aachen, Germany. ogressner(-atsign-)ukaachen.de

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't; Review

Journal: Hepatology (Baltimore, Md.) (Hepatology), published in United States. (Language: eng)

Reference: 2009-Sep; vol 50 (issue 3) : pp 970-8

Dates: Created 2009/09/02; Completed 2009/09/18;

PMID: 19610047, status: MEDLINE (last retrieval date: 9/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Acetylgalactosamine - analogs & derivatives; antagonists & inhibitors Animals Caffeine - metabolism; pharmacology Carcinoma, Hepatocellular - prevention & control Collagen Type I - biosynthesis Connective Tissue Growth Factor - antagonists & inhibitors; biosynthesis Humans

Liver - drug effects; metabolism Liver Neoplasms - prevention & control Proteasome Endopeptidase Complex - metabolism Smad2 Protein - physiology Theophylline - pharmacology Transforming Growth Factor beta - antagonists & inhibitors Xanthines - pharmacology

Associated Chemicals: Collagen Type I (0) ; SMAD2 protein, human (0) ; Smad2 Protein (0) ; Transforming Growth Factor beta (0) ; Xanthines (0) ; N-acetylgalactosamine 6-sulfate (10357-00-3) ; Connective Tissue Growth Factor (139568-91-5) ; methylxanthine (28109-92-4) ; Acetylgalactosamine (31022-50-1) ; Caffeine (58-08-2) ; Theophylline (58-55-9) ; 1,7-dimethylxanthine (611-59-6) ; Proteasome Endopeptidase Complex (EC 3.4.25.1)

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