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PMID: 20055532 Published · ppublish English Journal Article Review

The role of endothelin-1 in the pathogenesis of idiopathic pulmonary fibrosis.

BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy ·Vol. 24 ·No. 1 ·2010-02-01 ·Pages 49-54

Swigris JJ, Brown KK

Abstract

The endothelin system participates in a number of critical biologic pathways, including normal wound healing. In addition, emerging basic science, and animal and human data all suggest that endothelin-1 (EDN1, also known as ET-1) is a potentially important contributor in the pathobiology of fibrosing disorders, including those that affect the lung. For example, EDN1 drives fibroblast activation, proliferation, as well as differentiation into myofibroblasts - processes that lead to excessive collagen deposition. Patients with idiopathic pulmonary fibrosis (IPF) have increased levels of EDN1 in both their bronchoalveolar lavage fluid and lung tissue. Beyond this, rodent models suggest that endothelin receptor antagonists can limit bleomycin-induced lung fibrosis. This suggests a biologic rationale for the blockade of EDN1 to limit the evolution of lung fibrosis in humans. Initial results from a trial examining the efficacy of a dual endothelin receptor antagonist suggest that this approach may delay disease progression in a subset of patients with IPF.

MeSH Terms
Animals Bronchoalveolar Lavage Fluid/cytology Disease Models, Animal Endothelin-1/genetics,physiology Endothelins/physiology Humans Lung/pathology Pulmonary Fibrosis/genetics,pathology Wound Healing/physiology
Chemicals
Endothelin-1 Endothelins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Swigris Jeffrey J
Interstitial Lung Disease Program, National Jewish Health, Denver, Colorado 80206, USA. swigrisj@njc.org
Brown Kevin K
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Article Info
Journal
BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy
Abbr.
BioDrugs
ISSN
1179-190X
DOI
10.2165/11319550-000000000-00000
Email
swigrisj@njc.org
Published
2010-02-01
Pages
49-54
Language
English
Region
New Zealand
NLM ID
9705305
PMCID
PMC2855311
Subset
IM
Grants
NHLBI NIH HHS · K23 HL092227 · United States
NHLBI NIH HHS · K23 HL092227-01A2 · United States
External Links
PubMed source DOI: 10.2165/11319550-000000000-00000 PMC Full Text View journal details
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