Molecular targets in pulmonary fibrosis: the myofibroblast in focus
- PMID: 17934117
- DOI: 10.1378/chest.06-2568
Molecular targets in pulmonary fibrosis: the myofibroblast in focus
Abstract
Idiopathic pulmonary fibrosis (IPF) is one of a group of interstitial lung diseases that are characterized by excessive matrix deposition and destruction of the normal lung architecture. Long-term survival of IPF patients is poor, with a 5-year survival rate of only 20%. Despite a lack of evidence-based benefit, IPF has historically been treated with corticosteroids and/or cytotoxic agents such as prednisone. Given the poor efficacy of these drugs, novel therapeutic strategies are required for the management of IPF. This demands a better understanding of the molecular mechanisms underlying the pathogenesis and progression of this disease. The primary effector cell in fibrosis is the myofibroblast; these cells are highly synthetic for collagen, have a contractile phenotype, and are characterized by the presence of alpha-smooth muscle actin stress fibers. They may be derived by activation/proliferation of resident lung fibroblasts, epithelial-mesenchymal differentiation, or recruitment of circulating fibroblastic stem cells (fibrocytes). From a therapeutic viewpoint, interfering with the pathways that lead to myofibroblast expansion should be of considerable benefit in the treatment of IPF. This review will highlight some of the key molecules involved in this process and the clinical trials that have ensued.
Similar articles
-
Recent advances in molecular targets and treatment of idiopathic pulmonary fibrosis: focus on TGFbeta signaling and the myofibroblast.Curr Med Chem. 2009;16(11):1400-17. doi: 10.2174/092986709787846497. Curr Med Chem. 2009. PMID: 19355895 Review.
-
Negative regulation of myofibroblast differentiation by PTEN (Phosphatase and Tensin Homolog Deleted on chromosome 10).Am J Respir Crit Care Med. 2006 Jan 1;173(1):112-21. doi: 10.1164/rccm.200507-1058OC. Epub 2005 Sep 22. Am J Respir Crit Care Med. 2006. PMID: 16179636 Free PMC article.
-
RhoA signaling modulates cyclin D1 expression in human lung fibroblasts; implications for idiopathic pulmonary fibrosis.Respir Res. 2006 Jun 15;7(1):88. doi: 10.1186/1465-9921-7-88. Respir Res. 2006. PMID: 16776827 Free PMC article.
-
Fibroblast-matrix interplay: Nintedanib and pirfenidone modulate the effect of IPF fibroblast-conditioned matrix on normal fibroblast phenotype.Respirology. 2018 Aug;23(8):756-763. doi: 10.1111/resp.13287. Epub 2018 Mar 12. Respirology. 2018. PMID: 29532550
-
The role of circulating mesenchymal progenitor cells (fibrocytes) in the pathogenesis of pulmonary fibrosis.J Leukoc Biol. 2009 Nov;86(5):1111-8. doi: 10.1189/jlb.0309132. Epub 2009 Jul 6. J Leukoc Biol. 2009. PMID: 19581373 Free PMC article. Review.
Cited by
-
TGF-β-induced α-SMA expression is mediated by C/EBPβ acetylation in human alveolar epithelial cells.Mol Med. 2021 Mar 4;27(1):22. doi: 10.1186/s10020-021-00283-6. Mol Med. 2021. PMID: 33663392 Free PMC article.
-
ROCK and Rho: Promising therapeutic targets to ameliorate pulmonary fibrosis.Am J Pathol. 2015 Apr;185(4):909-12. doi: 10.1016/j.ajpath.2015.01.005. Epub 2015 Feb 14. Am J Pathol. 2015. PMID: 25687558 Free PMC article.
-
Mitochondrial One-Carbon Metabolism is Required for TGF-β-Induced Glycine Synthesis and Collagen Protein Production.bioRxiv [Preprint]. 2023 Nov 7:2023.11.07.566074. doi: 10.1101/2023.11.07.566074. bioRxiv. 2023. PMID: 37986788 Free PMC article. Preprint.
-
Shared and distinct mechanisms of fibrosis.Nat Rev Rheumatol. 2019 Dec;15(12):705-730. doi: 10.1038/s41584-019-0322-7. Epub 2019 Nov 11. Nat Rev Rheumatol. 2019. PMID: 31712723 Review.
-
The mTORC1/4E-BP1 axis represents a critical signaling node during fibrogenesis.Nat Commun. 2019 Jan 2;10(1):6. doi: 10.1038/s41467-018-07858-8. Nat Commun. 2019. PMID: 30602778 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
