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Defect matrix induces epithelial mesenchymal transition
Author(s) -
Weihrauch Dorothee,
Jones Deron Wade,
Warltier David C,
Pritchard Kirkwood Jr
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.524.6
Subject(s) - epithelial–mesenchymal transition , extracellular matrix , fibrosis , fibroblast , mesenchymal stem cell , proinflammatory cytokine , chemistry , microbiology and biotechnology , in vivo , pulmonary fibrosis , pathology , cancer research , biology , in vitro , medicine , immunology , downregulation and upregulation , inflammation , biochemistry , gene
One of the hallmarks of systemic scleroderma (SSc) is the increase in the production of extracellular matrix protein. We have previously shown that D4F, an ApoA1 mimetic, reduces the extent of fibrosis in the heart and decreases proinflammatory HDL and angiostatin levels in tight skin mice (Tsk −/+ mice), a model for SSc. To further understand the mechanisms of the process of fibrosis and lastly development of heart failure in SSc we studied the involvement of epicardial cells transitioning into fibroblasts, a process called epithelial mesenchymal transition (EMT). We performed immunohistochemistry using an antibody against the fibroblast marker FSP‐1 and an antibody against the transcription factor twist which is described to be involved in EMT. Epithelial transitioned into fibroblasts in vitro when grown on microfibers harvested from skin from Tsk −/+ mice compared to epithelial cells grown on microfibers from C57/BL6 mice. D4F treatment reduced the number of transitioning, and FSP‐1 positive epithelial cells but increased the expression of twist. In vivo we found epicardial cells in transition characterized by expressing higher levels of FSP‐1 in myocardium of TSK −/+ mice. In TSK −/+ myocardium twist protein levels were increased These data show that one of the contributors to fibrosis in the heart in SSc are epicardial cells transitioning into fibroblasts and that D4F reverses this process by increasing twist levels and promoting cell migration and tissue remodeling.