Injury triggers fascia fibroblast collective cell migration to drive scar formation through N-cadherin.
Injury triggers fascia fibroblast collective cell migration to drive scar formation through N-cadherin.
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DOI：
10.1038/s41467-020-19425-1
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发表时间：
2020-11-06
影响因子：
16.6
通讯作者：
Rinkevich Y
中科院分区：
文献类型：
--
作者：
Jiang D;Christ S;Correa-Gallegos D;Ramesh P;Kalgudde Gopal S;Wannemacher J;Mayr CH;Lupperger V;Yu Q;Ye H;Mück-Häusl M;Rajendran V;Wan L;Liu J;Mirastschijski U;Volz T;Marr C;Schiller HB;Rinkevich Y
当真皮下的皮下筋膜在手术或创伤性创伤后受伤时，疤痕更严重。在这里，我们提出了一个详细的分析筋膜细胞动员，通过使用深组织活体活成像的急性手术伤口，成纤维细胞谱系特异性转基因小鼠，皮肤筋膜外植体（疤痕样组织在一个盘子-SCAD）。我们观察到，损伤触发了筋膜成纤维细胞的群集样集体细胞迁移，逐渐收缩皮肤并形成疤痕。群集是筋膜成纤维细胞所独有的，并且需要N-钙粘蛋白的上调。群集和N-钙粘蛋白的表达都不存在于皮肤上层和口腔粘膜的成纤维细胞中，这些组织修复创伤，瘢痕最小。阻碍N-钙粘蛋白结合抑制群集和皮肤收缩，并导致SCAD和动物中瘢痕形成减少。因此，成纤维细胞群集和N-钙粘蛋白提供了在一系列医疗环境中减少筋膜动员和病理性纤维化反应的治疗途径。与浅表伤口相比，深层伤口会产生广泛的疤痕，但原因尚不清楚。在这里，作者使用离体形成的生理伤口和瘢痕的实时成像来显示筋膜成纤维细胞上调N-钙粘蛋白，从而允许协调的细胞迁移，从而驱动深部伤口的广泛瘢痕形成。
Scars are more severe when the subcutaneous fascia beneath the dermis is injured upon surgical or traumatic wounding. Here, we present a detailed analysis of fascia cell mobilisation by using deep tissue intravital live imaging of acute surgical wounds, fibroblast lineage-specific transgenic mice, and skin-fascia explants (scar-like tissue in a dish – SCAD). We observe that injury triggers a swarming-like collective cell migration of fascia fibroblasts that progressively contracts the skin and form scars. Swarming is exclusive to fascia fibroblasts, and requires the upregulation of N-cadherin. Both swarming and N-cadherin expression are absent from fibroblasts in the upper skin layers and the oral mucosa, tissues that repair wounds with minimal scar. Impeding N-cadherin binding inhibits swarming and skin contraction, and leads to reduced scarring in SCADs and in animals. Fibroblast swarming and N-cadherin thus provide therapeutic avenues to curtail fascia mobilisation and pathological fibrotic responses across a range of medical settings. Extensive scars develop in deep wounds as opposed to superficial wounds but it is unclear why. Here, the authors use live imaging of physiologic wounds and scars formed ex vivo to show that fascia fibroblasts upregulate N-cadherin allowing coordinated cell migration that drives extensive scar formation of deep wounds.
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DOI：
10.1126/science.aaa2151
发表时间：
2015-04-17
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Rinkevich Y;Walmsley GG;Hu MS;Maan ZN;Newman AM;Drukker M;Januszyk M;Krampitz GW;Gurtner GC;Lorenz HP;Weissman IL;Longaker MT
通讯作者：
Longaker MT
影响因子：
64.5
作者：
Ouspenskaia T;Matos I;Mertz AF;Fiore VF;Fuchs E
通讯作者：
Fuchs E
影响因子：
4.9
作者：
Burke, John P.;Cunningham, Michael F.;O'Connell, P. Ronan
通讯作者：
O'Connell, P. Ronan
DOI：
10.1002/cyto.a.23260
发表时间：
2018-03
期刊：
Cytometry. Part A : the journal of the International Society for Analytical Cytology
影响因子：
--
作者：
Lupperger V;Buggenthin F;Chapouton P;Marr C
通讯作者：
Marr C
影响因子：
8.8
作者：
Black M;Milewski D;Le T;Ren X;Xu Y;Kalinichenko VV;Kalin TV
通讯作者：
Kalin TV