The extracellular matrix modification in pulmonary fibrosis

The lung is a vital organ which allows gas exchanges between the external environment and the body. These gas exchanges take place in alveoli, formed by 2 cell types : pneumocytes I and II (Martinez et al., 2017).  The alveolar wall is supported by a basal membrane mainly composed of collagen IV and laminin (Burgstaller et al., 2017). Alveoli are surrounded by the interstitial space, mainly collagen I and III, fibronectin, elastin and hyaluronic acid. These molecules are secreted by the fibroblasts present in this space.  The pulmonary fibrosis is a chronic disease of lung interstitial tissues, mainly cause by aging, smoking, chronic viral infection or genetic mutations (Martinez et al., 2017).

Repeated lesions of alveolar epithelium can lead a deregulation of repair mechanisms, leading to interstitial tissues degradation and its replacement by scar tissue, formed as a rigid extracellular matrix. Indeed, in pulmonary fibrosis, the cells of the alveolar epithelium can be activated and produce various molecules, including the Transforming Growth Factor-β (TGF-β), the Connective Tissue Growth Factor, several metalloproteinases and chemokines, which stimulate myofibroblastes and matrix remodeling. The myofibroblasts play a major role in the establishment of pulmonary fibrosis, through the production of fibrillary collagen, fibronectin, tenascin-C and proteoglycans. The rigidity and remodeling of the extracellular matrix in the pulmonary fibrosis could participate to the abnormal cell behavior, the activation of fibroblasts and the accumulation of extracellular matrix, leading to a vicious cycle. This remodeling decreases gas exchanges’ efficiency, and thus can lead to breath deficiency and death.

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REFERENCES

Burgstaller, G., Oehrle, B., Gerckens, M., White, E.S., Schiller, H.B., and Eickelberg, O. (2017). The instructive extracellular matrix of the lung: basic composition and alterations in chronic lung disease. Eur Respir J 50, 1601805.

Martinez, F.J., Collard, H.R., Pardo, A., Raghu, G., Richeldi, L., Selman, M., Swigris, J.J., Taniguchi, H., and Wells, A.U. (2017). Idiopathic pulmonary fibrosis. Nat Rev Dis Primers 3, 17074.