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Matrix metalloproteinase gene delivery for liver fibrosis.

Abstract
The resolution of advanced liver fibrosis has been recently recognized to be possible, if the causative stimuli are successfully removed. However, whether complete resolution from cirrhosis, the end stage of liver fibrosis, can be achieved is still questionable. Delivery of interstitial collagenases, such as matrix metalloproteinase (MMP)-1, in the liver could be an attractive strategy to treat advanced hepatic fibrosis from the view point that the imbalance between too few interstitial collagenases and too many of their inhibitors is the main obstacle to the resolution from fibrosis. Remodeling of hepatic extracellular matrix by delivered interstitial collagenases also facilitates the disappearance of activated hepatic stellate cells, the main matrix-producing cells in the liver, and promotes the proliferation of hepatocytes. This review will focus on the impact of the gene delivery of MMPs for the treatment of advanced liver fibrosis while discussing other current therapeutic strategies for liver fibrosis, and on the need for the development of a safe and effective delivery system of MMPs.
AuthorsYuji Iimuro, David A Brenner
JournalPharmaceutical research (Pharm Res) Vol. 25 Issue 2 Pg. 249-58 (Feb 2008) ISSN: 0724-8741 [Print] United States
PMID17577645 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Anti-Inflammatory Agents
  • Matrix Metalloproteinases
Topics
  • Animals
  • Anti-Inflammatory Agents (therapeutic use)
  • Bone Marrow Transplantation
  • Gene Transfer Techniques
  • Genetic Therapy
  • Genetic Vectors
  • Humans
  • Liver Cirrhosis (etiology, therapy)
  • Matrix Metalloproteinases (genetics)

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