Absence of fibromodulin affects matrix composition, collagen deposition and cell turnover in healthy and fibrotic lung parenchyma

作者：Rydell Tormanen Kristina^*; Andreasson Kristofer; Hesselstrand Roger; Westergren Thorsson Gunilla

来源：Scientific Reports, 2014, 4(1): 6383.

DOI：10.1038/srep06383

The ECM exerts great effects on cells, and changed composition may therefore have profound impact. Small leucine-rich proteoglycans, e. g. fibromodulin, are essential in collagen assembly. Our aim was to investigate the role of fibromodulin in healthy and fibrotic lung parenchyma, theorizing that fibromodulin-deficient animals would be protected against fibrosis. Repeated subcutaneous bleomycin-injections were given to wild type and fibromodulin-deficient mice, inducing pulmonary fibrosis. Development of fibrosis, ECM composition, cell turnover and inflammatory responses were investigated. Fibromodulin-deficient animals were not protected from fibrosis, but the composition of the matrix was affected, with decreased Collagen I in fibromodulin-deficient animals, both in controls (0.07 +/- 0.04% vs. 0.18 +/- 0.07% tissue area) and after bleomycin (0.37 +/- 0.16% vs. 0.61 +/- 0.21% tissue area). Biglycan was increased in fibromodulin-deficient animals, whereas decorin was decreased. Furthermore, bleomycin increased cell turnover in wild type, but only proliferation in fibromodulin-deficient animals, resulting in hyperplasia. In addition, the bleomycin-induced immune response was affected in fibromodulin-deficient animals. We thus conclude that fibromodulin has a profound effect on ECM, both in healthy and fibrotic lung parenchyma, and may be providing a permissive microenvironment affecting cell turnover. Furthermore, this study highlights the need to acknowledge specific ECM components, when assessing tissue properties and ultimately cell behaviour.

• 出版日期2014-9-18