Periostin modulates myofibroblast differentiation during full-thickness cutaneous wound repair
Periostin modulates myofibroblast differentiation during full-thickness cutaneous wound repair
复制标题
DOI：
10.1242/jcs.087841
复制
发表时间：
2012-01-01
影响因子：
4
通讯作者：
Hamilton, Douglas W.
中科院分区：
文献类型：
--
作者：
Elliott, Christopher G.;Wang, Jian;Hamilton, Douglas W.
基质细胞蛋白骨膜蛋白在皮肤中表达。尽管人们假设骨膜蛋白有助于皮肤的稳态和修复，但这还没有得到直接的测试。为了评估骨膜蛋白对皮肤愈合的贡献，在骨膜蛋白敲除和野生型、性别匹配的对照组小鼠皮肤上创建了6毫米全层切除伤口。在野生型小鼠中，损伤后5-7天可有效诱导骨膜蛋白。在没有骨膜蛋白的情况下，第7天的伤口显示出肌成纤维细胞的显著减少，这可以通过肉芽组织中α -平滑肌肌动蛋白（α - sma）的表达来观察。通过电纺丝胶原支架递送重组人骨膜蛋白可恢复α - sma的表达。分离的野生型和敲除型真皮成纤维细胞在体外粘附或迁移方面没有差异；然而，在3D培养中，敲除骨膜蛋白的成纤维细胞显示出胶原基质收缩能力显著降低，并呈现树突状表型。重组骨膜蛋白恢复了骨膜蛋白缺陷成纤维细胞的细胞形态缺陷和基质收缩，其方式对中和性抗- 1整合素和FAK和Src抑制剂PP2敏感。我们认为骨膜蛋白通过促进肌成纤维细胞分化和收缩来促进伤口收缩。
The matricellular protein periostin is expressed in the skin. Although periostin has been hypothesized to contribute to dermal homeostasis and repair, this has not been directly tested. To assess the contribution of periostin to dermal healing, 6 mm full-thickness excisional wounds were created in the skin of periostin-knockout and wild-type, sex-matched control mice. In wild-type mice, periostin was potently induced 5-7 days after wounding. In the absence of periostin, day 7 wounds showed a significant reduction in myofibroblasts, as visualized by expression of alpha-smooth muscle actin (alpha-SMA) within the granulation tissue. Delivery of recombinant human periostin by electrospun collagen scaffolds restored alpha-SMA expression. Isolated wild-type and knockout dermal fibroblasts did not differ in in vitro assays of adhesion or migration; however, in 3D culture, periostin-knockout fibroblasts showed a significantly reduced ability to contract a collagen matrix, and adopted a dendritic phenotype. Recombinant periostin restored the defects in cell morphology and matrix contraction displayed by periostin-deficient fibroblasts in a manner that was sensitive to a neutralizing anti-beta 1-integrin and to the FAK and Src inhibitor PP2. We propose that periostin promotes wound contraction by facilitating myofibroblast differentiation and contraction.