Matrix Abnormalities in Pulmonary Fibrosis

Overview

Journal Eur Respir Rev

Specialty Pulmonary Medicine

Date 2018 Jun 29

PMID 29950306

Citations 117

Authors

Chandak Upagupta

Chiko Shimbori

Rahmah Alsilmi

Martin Kolb

Affiliations

Soon will be listed here.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a devastating, progressive disease, marked by excessive scarring, which leads to increased tissue stiffness, loss in lung function and ultimately death. IPF is characterised by progressive fibroblast and myofibroblast proliferation, and extensive deposition of extracellular matrix (ECM). Myofibroblasts play a key role in ECM deposition. Transforming growth factor (TGF)-β1 is a major growth factor involved in myofibroblast differentiation, and the creation of a profibrotic microenvironment. There is a strong link between increased ECM stiffness and profibrotic changes in cell phenotype and differentiation. The activation of TGF-β1 in response to mechanical stress from a stiff ECM explains some of the influence of the tissue microenvironment on cell phenotype and function. Understanding the close relationship between cells and their surrounding microenvironment will ultimately facilitate better management strategies for IPF.

Citing Articles

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Novel Integration of Spatial and Single-Cell Omics Data Sets Enables Deeper Insights into IPF Pathogenesis.

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References

Xaubet A, Marin-Arguedas A, Lario S, Ancochea J, Morell F, Ruiz-Manzano J . Transforming growth factor-beta1 gene polymorphisms are associated with disease progression in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2003; 168(4):431-5. DOI: 10.1164/rccm.200210-1165OC. View

Kulkarni T, OReilly P, Antony V, Gaggar A, Thannickal V . Matrix Remodeling in Pulmonary Fibrosis and Emphysema. Am J Respir Cell Mol Biol. 2016; 54(6):751-60. PMC: 4942216. DOI: 10.1165/rcmb.2015-0166PS. View

Chien J, Richards T, Gibson K, Zhang Y, Lindell K, Shao L . Serum lysyl oxidase-like 2 levels and idiopathic pulmonary fibrosis disease progression. Eur Respir J. 2013; 43(5):1430-8. DOI: 10.1183/09031936.00141013. View

Selman M, Pardo A . Revealing the pathogenic and aging-related mechanisms of the enigmatic idiopathic pulmonary fibrosis. an integral model. Am J Respir Crit Care Med. 2014; 189(10):1161-72. DOI: 10.1164/rccm.201312-2221PP. View

Xu J, Lamouille S, Derynck R . TGF-beta-induced epithelial to mesenchymal transition. Cell Res. 2009; 19(2):156-72. PMC: 4720263. DOI: 10.1038/cr.2009.5. View

Schmidt M, Sun G, Stacey M, Mori L, Mattoli S . Identification of circulating fibrocytes as precursors of bronchial myofibroblasts in asthma. J Immunol. 2003; 171(1):380-9. DOI: 10.4049/jimmunol.171.1.380. View

Liu F, Lagares D, Choi K, Stopfer L, Marinkovic A, Vrbanac V . Mechanosignaling through YAP and TAZ drives fibroblast activation and fibrosis. Am J Physiol Lung Cell Mol Physiol. 2014; 308(4):L344-57. PMC: 4329470. DOI: 10.1152/ajplung.00300.2014. View

Kadler K, Hill A, Canty-Laird E . Collagen fibrillogenesis: fibronectin, integrins, and minor collagens as organizers and nucleators. Curr Opin Cell Biol. 2008; 20(5):495-501. PMC: 2577133. DOI: 10.1016/j.ceb.2008.06.008. View

Serini G, Bochaton-Piallat M, Ropraz P, Geinoz A, Borsi L, Zardi L . The fibronectin domain ED-A is crucial for myofibroblastic phenotype induction by transforming growth factor-beta1. J Cell Biol. 1998; 142(3):873-81. PMC: 2148176. DOI: 10.1083/jcb.142.3.873. View

10.

Carloni A, Poletti V, Fermo L, Bellomo N, Chilosi M . Heterogeneous distribution of mechanical stress in human lung: a mathematical approach to evaluate abnormal remodeling in IPF. J Theor Biol. 2013; 332:136-40. DOI: 10.1016/j.jtbi.2013.04.038. View

11.

KUHN 3rd C, Boldt J, King Jr T, Crouch E, Vartio T, McDonald J . An immunohistochemical study of architectural remodeling and connective tissue synthesis in pulmonary fibrosis. Am Rev Respir Dis. 1989; 140(6):1693-703. DOI: 10.1164/ajrccm/140.6.1693. View

12.

Selman M, Pardo A . Alveolar epithelial cell disintegrity and subsequent activation: a key process in pulmonary fibrosis. Am J Respir Crit Care Med. 2012; 186(2):119-21. DOI: 10.1164/rccm.201206-0997ED. View

13.

Barry-Hamilton V, Spangler R, Marshall D, McCauley S, Rodriguez H, Oyasu M . Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a pathologic microenvironment. Nat Med. 2010; 16(9):1009-17. DOI: 10.1038/nm.2208. View

14.

Zielonka T, Demkow U, Radzikowska E, Bialas B, Filewska M, Zycinska K . Angiogenic activity of sera from interstitial lung disease patients in relation to pulmonary function. Eur J Med Res. 2010; 15 Suppl 2:229-34. PMC: 4360317. DOI: 10.1186/2047-783x-15-s2-229. View

15.

Martinez F, Flaherty K . Pulmonary function testing in idiopathic interstitial pneumonias. Proc Am Thorac Soc. 2006; 3(4):315-21. PMC: 2658684. DOI: 10.1513/pats.200602-022TK. View

16.

Border W, Noble N . Transforming growth factor beta in tissue fibrosis. N Engl J Med. 1994; 331(19):1286-92. DOI: 10.1056/NEJM199411103311907. View

17.

Janostiak R, Pataki A, Brabek J, Rosel D . Mechanosensors in integrin signaling: the emerging role of p130Cas. Eur J Cell Biol. 2014; 93(10-12):445-54. DOI: 10.1016/j.ejcb.2014.07.002. View

18.

Akhmetshina A, Dees C, Pileckyte M, Szucs G, Spriewald B, Zwerina J . Rho-associated kinases are crucial for myofibroblast differentiation and production of extracellular matrix in scleroderma fibroblasts. Arthritis Rheum. 2008; 58(8):2553-64. DOI: 10.1002/art.23677. View

19.

Olsen K, Sapinoro R, Kottmann R, Kulkarni A, Iismaa S, Johnson G . Transglutaminase 2 and its role in pulmonary fibrosis. Am J Respir Crit Care Med. 2011; 184(6):699-707. PMC: 3208598. DOI: 10.1164/rccm.201101-0013OC. View

20.

Georges P, Hui J, Gombos Z, McCormick M, Wang A, Uemura M . Increased stiffness of the rat liver precedes matrix deposition: implications for fibrosis. Am J Physiol Gastrointest Liver Physiol. 2007; 293(6):G1147-54. DOI: 10.1152/ajpgi.00032.2007. View