The matrix protein Fibulin-5 is at the interface of tissue stiffness and inflammation in fibrosis.
The matrix protein Fibulin-5 is at the interface of tissue stiffness and inflammation in fibrosis.
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DOI：
10.1038/ncomms9574
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发表时间：
2015-10-15
影响因子：
16.6
通讯作者：
Jamora C
中科院分区：
文献类型：
--
作者：
Nakasaki M;Hwang Y;Xie Y;Kataria S;Gund R;Hajam EY;Samuel R;George R;Danda D;M J P;Nakamura T;Shen Z;Briggs S;Varghese S;Jamora C
纤维化是一种广泛存在的疾病，其中细胞外基质（ECM）的过度沉积损害组织功能。尽管其潜在机制大多未知，但基质硬度越来越被认为是纤维化的贡献者，而不仅仅是疾病的表现。在这里，我们表明，Fibulin-5，弹性纤维成分的损失，不仅降低组织硬度，而且还减少炎症反应，并废除皮肤纤维化小鼠模型中的纤维化表型。增加基质硬度将炎症反应提高到阈值水平以上，独立于TGF-β，以刺激成纤维细胞进一步分泌ECM并促进纤维化的进展。这些结果表明，Fibulin-5可能是一个治疗靶点，以缩短这种促纤维化反馈回路。 细胞外基质的僵硬被认为是导致病理性皮肤纤维化的原因。在这里，作者将弹性纤维蛋白Fibulin-5确定为介导皮肤硬化向纤维化转变的联系和潜在治疗靶点。
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. Stiffness in the extracellular matrix is thought to contribute to pathological cutaneous fibrosis. Here, the authors identify the elastic fibre protein Fibulin-5 as a link and potential therapeutic target mediating the transition of cutaneous stiffening to fibrosis.