Novel mediators of idiopathic pulmonary fibrosis
- 31 August 2022
- journal article
- review article
- Published by Portland Press Ltd. in Clinical Science
- Vol. 136 (16), 1229-1240
- https://doi.org/10.1042/cs20210878
Abstract
Fibrosis involving the lung may occur in many settings, including in association with known environmental agents, connective tissue diseases, and exposure to drugs or radiation therapy. The most common form is referred to as ‘idiopathic’ since a causal agent or specific association has not been determined; the strongest risk factor for idiopathic pulmonary fibrosis is aging. Emerging studies indicate that targeting certain components of aging biology may be effective in mitigating age-associated fibrosis. While transforming growth factor-β1 (TGF-β1) is a central mediator of fibrosis in almost all contexts, and across multiple organs, it is not feasible to target this canonical pathway at the ligand–receptor level due to the pleiotropic nature of its actions; importantly, its homeostatic roles as a tumor-suppressor and immune-modulator make this an imprudent strategy. However, defining targets downstream of its receptor(s) that mediate fibrogenesis, while relatively dispenable for tumor- and immune-suppressive functions may aid in developing safer and more effective therapies. In this review, we explore molecular targets that, although TGF-β1 induced/activated, may be relatively more selective in mediating tissue fibrosis. Additionally, we explore epigenetic mechanisms with global effects on the fibrogenic process, as well as metabolic pathways that regulate aging and fibrosis.Keywords
This publication has 113 references indexed in Scilit:
- Histone modifications are responsible for decreased Fas expression and apoptosis resistance in fibrotic lung fibroblastsCell Death & Disease, 2013
- Therapeutic Value of Small Molecule Inhibitor to Plasminogen Activator Inhibitor–1 for Lung FibrosisAmerican Journal of Respiratory Cell and Molecular Biology, 2012
- miR-29 Is a Major Regulator of Genes Associated with Pulmonary FibrosisAmerican Journal of Respiratory Cell and Molecular Biology, 2011
- Reversible differentiation of myofibroblasts by MyoDExperimental Cell Research, 2011
- Histone Deacetylase: A Potential Therapeutic Target for Fibrotic DisordersThe Journal of pharmacology and experimental therapeutics, 2010
- NADPH oxidase-4 mediates myofibroblast activation and fibrogenic responses to lung injuryNature Medicine, 2009
- Telomere Shortening in Familial and Sporadic Pulmonary FibrosisAmerican Journal of Respiratory and Critical Care Medicine, 2008
- Myofibroblast contraction activates latent TGF-β1 from the extracellular matrixThe Journal of cell biology, 2007
- Adult-onset pulmonary fibrosis caused by mutations in telomeraseProceedings of the National Academy of Sciences of the United States of America, 2007
- CpG Islands in vertebrate genomesJournal of Molecular Biology, 1987