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


CONCLUSIONS
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.
Gharaee-Kermani
Mehrnaz
M
University of Michigan Medical School, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, 2215 Fuller Road, 11R, Ann Arbor, MI 48105, USA. nazy@umich.edu
Hu
Biao
B
Phan
Sem H
SH
Gyetko
Margaret R
MR
D000347:Afibrinogenemia / Q000150:complications / Q000235:genetics; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use*; D001761:Bleomycin / Q000633:toxicity; D002921:Cicatrix / Q000209:etiology / Q000517:prevention & control; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004789:Enzyme Activation; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010958:Plasminogen / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000502:physiology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D011817:Rabbits; D051381:Rats; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000502:physiology; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator / Q000737:chemistry / Q000502:physiology*
D000925:Anticoagulants; D005343:Fibrinolytic Agents; C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; C524899:Plaur protein, mouse; C524900:Plaur protein, rat; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; C051321:SERPINE1 protein, human; D001761:Bleomycin; D010958:Plasminogen; D003094:Collagen; D014568:Urokinase-Type Plasminogen Activator