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Publication : The matrix protein Fibulin-5 is at the interface of tissue stiffness and inflammation in fibrosis.

First Author  Nakasaki M Year  2015
Journal  Nat Commun Volume  6
Pages  8574 PubMed ID  26469761
Mgi Jnum  J:227630 Mgi Id  MGI:5702343
Doi  10.1038/ncomms9574 Citation  Nakasaki M, et al. (2015) The matrix protein Fibulin-5 is at the interface of tissue stiffness and inflammation in fibrosis. Nat Commun 6:8574
abstractText  Fibrosis is a pervasive disease in which the excessive deposition of extracellular matrix (ECM) compromises tissue function. Although the underlying mechanisms are mostly unknown, matrix stiffness is increasingly appreciated as a contributor to fibrosis rather than merely a manifestation of the disease. Here we show that the loss of Fibulin-5, an elastic fibre component, not only decreases tissue stiffness, but also diminishes the inflammatory response and abrogates the fibrotic phenotype in a mouse model of cutaneous fibrosis. Increasing matrix stiffness raises the inflammatory response above a threshold level, independent of TGF-beta, to stimulate further ECM secretion from fibroblasts and advance the progression of fibrosis. These results suggest that Fibulin-5 may be a therapeutic target to short-circuit this profibrotic feedback loop.
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