Spatial Gradients of E-Cadherin and Fibronectin in TGF-β1-Treated Epithelial Colonies Are Independent of Fibronectin Fibril Assembly.
Spatial Gradients of E-Cadherin and Fibronectin in TGF-β1-Treated Epithelial Colonies Are Independent of Fibronectin Fibril Assembly.
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DOI：
10.3390/ijms24076679
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发表时间：
2023-04-03
影响因子：
5.6
通讯作者：
Lemmon, Christopher A.
中科院分区：
文献类型：
--
作者：
Griggs, Lauren A.;Lemmon, Christopher A.
上皮细胞向间充质细胞转化（EMT）是一个动态的形态发生过程，其特征在于上皮细胞向能动的和通常侵袭性间充质细胞表型的表型转变。我们以前已经证明，EMT与细胞外基质蛋白纤连蛋白（FN）组装成不溶性粘弹性原纤维的增加有关。我们还证明了转化生长因子-1（TGF-1）定位于FN原纤维，FN组装的破坏或TGF-1定位于FN原纤维的破坏减弱了EMT。以前的研究表明，TGF-1诱导FN岛上培养的乳腺上皮细胞EMT的空间梯度，在岛的自由边缘的细胞优先进行EMT。在目前的工作中，我们试图研究：（a）FN原纤维组装是否也响应于TGF-1的空间模式，以及（B）FN原纤维抑制对E-钙粘蛋白和FN原纤维形成的空间梯度有什么影响。我们证明，乳腺上皮细胞培养的正方形micropatterns有较少的E-钙粘蛋白含adherens连接和组装更多的FN纤维在周边的micropatterns在响应增加TGF-1浓度，表明TGF-1诱导的空间梯度的E-钙粘蛋白和FN纤维。FN原纤维组装的抑制在全球范围内减少了含E-钙粘蛋白的粘附连接和FN原纤维形成，但没有消除空间梯度。这表明FN的全局抑制降低了FN原纤维形成和含E-钙粘蛋白的粘附连接的程度，但并没有消除两者的空间梯度，这表明EMT和FN原纤维形成的空间梯度受到其他因素的影响。
Epithelial to Mesenchymal Transition (EMT) is a dynamic, morphogenetic process characterized by a phenotypic shift in epithelial cells towards a motile and often invasive mesenchymal phenotype. We have previously demonstrated that EMT is associated with an increase in assembly of the extracellular matrix protein fibronectin (FN) into insoluble, viscoelastic fibrils. We have also demonstrated that Transforming Growth Factor-1 (TGF-1) localizes to FN fibrils, and disruption of FN assembly or disruption of TGF-1 localization to FN fibrils attenuates EMT. Previous studies have shown that TGF-1 induces spatial gradients of EMT in mammary epithelial cells cultured on FN islands, with cells at free edges of the island preferentially undergoing EMT. In the current work, we sought to investigate: (a) whether FN fibril assembly is also spatially patterned in response to TGF-1, and (b) what effects FN fibril inhibition has on spatial gradients of E-Cadherin and FN fibrillogenesis. We demonstrate that mammary epithelial cells cultured on square micropatterns have fewer E-Cadherin-containing adherens junctions and assemble more FN fibrils at the periphery of the micropattern in response to increasing TGF-1 concentration, indicating that TGF-1 induces a spatial gradient of both E-Cadherin and FN fibrils. Inhibition of FN fibril assembly globally diminished E-Cadherin-containing adherens junctions and FN fibrillogenesis, but did not eliminate the spatial gradient of either. This suggests that global inhibition of FN reduces the degree of both FN fibrillogenesis and E-Cadherin-containing adherens junctions, but does not eliminate the spatial gradient of either, suggesting that spatial gradients of EMT and FN fibrillogenesis are influenced by additional factors.
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DOI：
10.1039/c5ib00217f
发表时间：
2015-11
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Scott LE;Mair DB;Narang JD;Feleke K;Lemmon CA
通讯作者：
Lemmon CA
影响因子：
3.3
作者：
Ramirez-San Juan GR;Oakes PW;Gardel ML
通讯作者：
Gardel ML
影响因子：
--
作者：
Muncie JM;Weaver VM
通讯作者：
Weaver VM
影响因子：
8
作者：
通讯作者：
--
影响因子：
3.4
作者：
Lemmon, Christopher A.;Chen, Christopher S.;Romer, Lewis H.
通讯作者：
Romer, Lewis H.