The role of urokinase in idiopathic pulmonary fibrosis and implication for therapy

Expert Opin Investig Drugs. 2008 Jun;17(6):905-16. doi: 10.1517/13543784.17.6.905.

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and frequently fatal form of interstitial lung disease for which there are no proven drug therapies. The pathogenesis of IPF is complex and the urokinase-type plasminogen activator (uPA)/plasminogen system participates in the repair process. The balance between the activating enzyme uPA, and its inhibitor PAI-1, is a critical determinant of the amount of scar development that follows.

Objective: To address the role of urokinase in the pathogenesis of pulmonary fibrosis and its implications for therapy.

Methods: We reviewed a spectrum of therapeutic strategies and focused on fibrinolytic and anticoagulant drugs for IPF patients.

Results/conclusion: There is currently a search for new pharmacotherapeutic agents that may modulate the fibrogenic pathways in IPF. Either blocking PAI-1 or using uPA itself may be a promising new therapeutic strategy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Afibrinogenemia / complications
  • Afibrinogenemia / genetics
  • Animals
  • Anticoagulants / pharmacology
  • Anticoagulants / therapeutic use*
  • Bleomycin / toxicity
  • Cicatrix / etiology
  • Cicatrix / prevention & control
  • Collagen / metabolism
  • Disease Models, Animal
  • Drug Design
  • Drug Evaluation, Preclinical
  • Enzyme Activation
  • Fibrinolytic Agents / pharmacology
  • Fibrinolytic Agents / therapeutic use*
  • Humans
  • Mice
  • Mice, Knockout
  • Plasminogen / metabolism
  • Plasminogen Activator Inhibitor 1 / physiology
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / drug therapy*
  • Pulmonary Fibrosis / enzymology
  • Pulmonary Fibrosis / pathology
  • Rabbits
  • Rats
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / physiology
  • Receptors, Urokinase Plasminogen Activator
  • Urokinase-Type Plasminogen Activator / chemistry
  • Urokinase-Type Plasminogen Activator / physiology*

Substances

  • Anticoagulants
  • Fibrinolytic Agents
  • PLAUR protein, human
  • Plasminogen Activator Inhibitor 1
  • Plaur protein, mouse
  • Plaur protein, rat
  • Receptors, Cell Surface
  • Receptors, Urokinase Plasminogen Activator
  • SERPINE1 protein, human
  • Bleomycin
  • Plasminogen
  • Collagen
  • Urokinase-Type Plasminogen Activator