BACKGROUND/AIMS: The development of liver cirrhosis can be described as a process of tissue remodeling, which involves increased matrix turnover. In order to determine whether the expression of tissue inhibitors of metalloproteinases (TIMPs) reflects these changes and can be used as a marker for the activity of ongoing fibrosis, we studied TIMP-1, 2 and -3 in liver and serum/plasma of patients with chronic hepatitis C, hepatitis C virus-induced cirrhosis and healthy controls. METHODOLOGY: Northern and Western blot analysis, reverse transcriptase polymerase chain reaction and ELISA measurements were performed. RESULTS: Reverse transcriptase polymerase chain reaction showed transcripts of all 3 TIMPs in liver tissue. TIMP-1 and -2 were also detectable in lymphocytes and granulocytes, which did not contain any TIMP-3. mRNA for TIMP-1 and -3, but not for TIMP-2, was detectable by Northern blot in normal human liver and increased in fibrosis and cirrhosis. Western blotting demonstrated the presence of all 3 TIMP proteins in healthy liver. TIMP-1 and TIMP-2 levels increased, but TIMP-3 was unchanged in cirrhosis compared to normal tissue. ELISA studies showed that the increase of TIMP-1 occurred only in advanced cirrhosis, while levels did not elevate in chronic hepatitis with or without fibrosis. In plasma, some of the cirrhotic patients had very high TIMP-1 values, while mean circulating TIMP-1 levels were not significantly different between controls, hepatitis C and cirrhotic patients. Serum TIMP-2 levels were higher in chronic hepatitis and cirrhosis than in controls, but did not differ between patients with or without histologic fibrosis. CONCLUSIONS: In normal human liver there is expression of all 3 TIMPs studied. The amount of hepatic TIMP-1 protein increases late in the fibrotic process, and there is a weak correlation between the activity of fibroproliferation and hepatic or circulating amounts of TIMP-1. Currently there is no evidence that measurement of TIMP-2 and TIMP-3 in liver or blood improves diagnosis of fibroproliferation in chronic hepatitis C.
BACKGROUND/AIMS: The development of liver cirrhosis can be described as a process of tissue remodeling, which involves increased matrix turnover. In order to determine whether the expression of tissue inhibitors of metalloproteinases (TIMPs) reflects these changes and can be used as a marker for the activity of ongoing fibrosis, we studied TIMP-1, 2 and -3 in liver and serum/plasma of patients with chronic hepatitis C, hepatitis C virus-induced cirrhosis and healthy controls. METHODOLOGY: Northern and Western blot analysis, reverse transcriptase polymerase chain reaction and ELISA measurements were performed. RESULTS: Reverse transcriptase polymerase chain reaction showed transcripts of all 3 TIMPs in liver tissue. TIMP-1 and -2 were also detectable in lymphocytes and granulocytes, which did not contain any TIMP-3. mRNA for TIMP-1 and -3, but not for TIMP-2, was detectable by Northern blot in normal human liver and increased in fibrosis and cirrhosis. Western blotting demonstrated the presence of all 3 TIMP proteins in healthy liver. TIMP-1 and TIMP-2 levels increased, but TIMP-3 was unchanged in cirrhosis compared to normal tissue. ELISA studies showed that the increase of TIMP-1 occurred only in advanced cirrhosis, while levels did not elevate in chronic hepatitis with or without fibrosis. In plasma, some of the cirrhotic patients had very high TIMP-1 values, while mean circulating TIMP-1 levels were not significantly different between controls, hepatitis C and cirrhotic patients. Serum TIMP-2 levels were higher in chronic hepatitis and cirrhosis than in controls, but did not differ between patients with or without histologic fibrosis. CONCLUSIONS: In normal human liver there is expression of all 3 TIMPs studied. The amount of hepatic TIMP-1 protein increases late in the fibrotic process, and there is a weak correlation between the activity of fibroproliferation and hepatic or circulating amounts of TIMP-1. Currently there is no evidence that measurement of TIMP-2 and TIMP-3 in liver or blood improves diagnosis of fibroproliferation in chronic hepatitis C.
Authors: Armanda Casrouge; Jérémie Decalf; Mina Ahloulay; Cyril Lababidi; Hala Mansour; Anaïs Vallet-Pichard; Vincent Mallet; Estelle Mottez; James Mapes; Arnaud Fontanet; Stanislas Pol; Matthew L Albert Journal: J Clin Invest Date: 2010-12-22 Impact factor: 14.808
Authors: Timo Rath; Lisa Hage; Marion Kügler; Katrin Menendez Menendez; Reinhart Zachoval; Lutz Naehrlich; Richard Schulz; Martin Roderfeld; Elke Roeb Journal: PLoS One Date: 2013-03-14 Impact factor: 3.240
Authors: Oh Sang Kwon; Hyuk Sang Jung; Kyung Sook Bae; Young Kul Jung; Yeon Suk Kim; Duck Joo Choi; Yun Soo Kim; Ju Hyun Kim Journal: Gut Liver Date: 2012-04-17 Impact factor: 4.519