IMR Press / FBL / Volume 7 / Issue 4 / DOI: 10.2741/pardo

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Molecular mechanisms of pulmonary fibrosis
Show Less
1 Facultad de Ciencias, Universidad Nacional Autónoma de México. Apartado Postal 21-630. Coyoacan; México DF, 04000, México
2 Instituto Nacional de Enfermedades Respiratorias, Tlalpan 4502; México DF, 14080, México
Academic Editor:Marcos Rojkind
Front. Biosci. (Landmark Ed) 2002, 7(4), 1743–1761; https://doi.org/10.2741/pardo
Published: 1 August 2002
(This article belongs to the Special Issue From regeneration to scar formation)
Abstract

Pulmonary fibrosis is the end-point of a numerous and heterogeneous group of disorders known as interstitial lung diseases (ILD). Lung fibrotic remodeling is characterized by fibroblast/myofibroblast activation, and excessive extracellular matrix accumulation leading to progressive organ dysfunction and usually terminal outcome. Treatment is largely ineffective primarily because few of the molecular mechanisms have been well defined to design appropriate targets for therapy. While the pathogenesis is incompletely understood, a growing body of evidence suggests two different pathogenic routes for developing pulmonary fibrosis. The inflammatory pathway, where a shift to the so-called T-helper 2 type cytokine networks is critical, and the epithelial pathway represented by idiopathic pulmonary fibrosis, by far the most aggressive ILD. In this pathway the inflammatory process is irrelevant, and the physiopathology seems to be dominated by epithelial cell injury and activation. Both routes may trigger a number of cytokines/growth factors inducing fibroblast migration/proliferation and phenotype change to myofibroblasts, with a consequent accumulation of extracellular matrix. An imbalance in matrix metalloproteinase/tissue inhibitors of metalloproteinases may contribute to alteration in extracellular matrix turnover and remodeling. This review will focus in some of the mechanisms involved in both prefibrotic pathways, as well as those involved in fibroblast activation and abnormal matrix deposition.

Keywords
Fibroblasts
Epithelial Cells
Cytokines
Chemokines
Cell Adhesion Molecules
Extracellular Matrix
Matrix Metalloproteinases
TIMP
Review
Share
Back to top