Periostin and matrix stiffness combine to regulate myofibroblast differentiation and fibronectin synthesis during palatal healing.
Periostin and matrix stiffness combine to regulate myofibroblast differentiation and fibronectin synthesis during palatal healing.
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骨膜素和基质刚度结合起来调节pa骨愈合过程中肌纤维细胞的分化和纤连蛋白合成。
DOI：
10.1016/j.matbio.2020.07.002
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Hamilton DW
中科院分区：
文献类型：
--
作者：
Nikoloudaki G;Snider P;Simmons O;Conway SJ;Hamilton DW
虽然基质细胞蛋白骨膜蛋白在皮肤和牙龈愈合中显著上调，但它在肌成纤维细胞分化和基质合成中分别发挥着截然不同的作用。腭愈合与瘢痕有关，瘢痕可改变或限制上颌骨生长，但骨膜素在腭愈合中的表达模式和作用尚不清楚。采用骨膜蛋白敲除（Postn−/−）和野生型（WT）小鼠，通过硬腭1.5 mm全层切除伤口研究骨膜蛋白对腭愈合的贡献。在WT小鼠中，骨膜蛋白在损伤后6天上调，mRNA水平在第12天达到峰值。与WT小鼠相比，骨膜蛋白基因缺失显著降低了伤口愈合率。缺骨膜蛋白会降低伤口修复关键基因α-SMA/acta2、纤维连接蛋白和βigh3的mRNA水平。通过对成纤维细胞特异性因子-1、波形蛋白和巨噬细胞标记物精氨酸酶-1和iNOS的免疫荧光染色，成纤维细胞和炎症细胞的募集也在post - / -小鼠中受损，但在WT小鼠中没有。将从小鼠硬腭分离的腭成纤维细胞培养在不同硬度的胶原凝胶和预制硅基质上。后n - / -成纤维细胞收缩胶原凝胶的能力显著降低，这是通过外源性添加重组骨膜蛋白来恢复的。随着硬度的增加，后n−/−成纤维细胞逐渐分化为肌成纤维细胞，但分化程度与WT不同。Rac的药物抑制恢复了后n−/−细胞的肌成纤维细胞表型缺陷。低刚度底物（0.2 kPa）导致WT细胞中纤维连接蛋白的上调，这一效应在后n−/−细胞中显著降低。定量免疫染色检测血管素和整合素粘附显示，在mpfb中，局灶性和纤维性粘附的形成需要骨膜蛋白。我们的研究结果表明，在腭愈合过程中，骨膜蛋白通过整合素β1/RhoA途径调节肌成纤维细胞的分化和收缩，并以ECM刚度依赖的方式调节纤维连接蛋白的合成。
Although the matricellular protein periostin is prominently upregulated in skin and gingival healing, it plays contrasting roles in myofibroblast differentiation and matrix synthesis respectively. Palatal healing is associated with scarring that can alter or restrict maxilla growth, but the expression pattern and contribution of periostin in palatal healing is unknown. Using periostin-knockout (Postn−/−) and wild-type (WT) mice, the contribution of periostin to palatal healing was investigated through 1.5 mm full-thickness excisional wounds in the hard palate. In WT mice, periostin was upregulated 6 days post-wounding, with mRNA levels peaking at day 12. Genetic deletion of periostin significantly reduced wound closure rates compared to WT mice. Absence of periostin reduced mRNA levels of pivotal genes in wound repair, including α-SMA/acta2, fibronectin and βigh3. Recruitment of fibroblasts and inflammatory cells, as visualized by immunofluorescent staining for fibroblast specific factor-1, vimentin, and macrophages markers Arginase-1 and iNOS was also impaired in Postn−/−, but not WT mice. Palatal fibroblasts isolated from the hard palate of mice were cultured on collagen gels and prefabricated silicon substrates with varying stiffness. Postn−/− fibroblasts showed a significantly reduced ability to contract a collagen gel, which was rescued by the exogenous addition of recombinant periostin. As the stiffness increased, Postn−/− fibroblasts increasingly differentiated into myofibroblasts, but not to the same degree as the WT. Pharmacological inhibition of Rac rescued the deficient myofibroblastic phenotype of Postn−/− cells. Low stiffness substrates (0.2 kPa) resulted in upregulation of fibronectin in WT cells, an effect which was significantly reduced in Postn−/− cells. Quantification of immunostaining for vinculin and integrinb1 adhesions revealed that Periostin is required for the formation of focal and fibrillar adhesions in mPFBs. Our results suggest that periostin modulates myofibroblast differentiation and contraction via integrinβ1/RhoA pathway, and fibronectin synthesis in an ECM stiffness dependent manner in palatal healing.
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影响因子：
6.5
作者：
Achterberg, Volker F.;Buscemi, Lara;Hinz, Boris
通讯作者：
Hinz, Boris
DOI：
10.1016/s0006-291x(02)00576-4
发表时间：
2002-06-28
影响因子：
3.1
作者：
Bae, JS;Lee, SH;Kim, IS
通讯作者：
Kim, IS
影响因子：
1.9
作者：
Cornelissen, AMH;Maltha, JC;Kuijpers-Jagtman, AM
通讯作者：
Kuijpers-Jagtman, AM
影响因子：
4
作者：
Elliott, Christopher G.;Wang, Jian;Hamilton, Douglas W.
通讯作者：
Hamilton, Douglas W.
DOI：
10.1083/jcb.200205014
发表时间：
2002-12-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
Danen EH;Sonneveld P;Brakebusch C;Fassler R;Sonnenberg A
通讯作者：
Sonnenberg A