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

TitleThe matrix protein Fibulin-5 is at the interface of tissue stiffness and inflammation in fibrosis.
Publication TypeJournal Article
Year of Publication2015
AuthorsM Nakasaki, Y Hwang, Y Xie, S Kataria, R Gund, EY Hajam, R Samuel, R George, D Danda, P M. J, T Nakamura, Z Shen, S Briggs, S Varghese, and C Jamora
JournalNature Communications
Volume6
Start Page8574
Date Published10/2015
Abstract

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-β, 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.

DOI10.1038/ncomms9574
Short TitleNature Communications