TGF-β-induced activation of conjunctival fibroblasts is modulated by FGF-2 and substratum stiffness.
TGF-β-induced activation of conjunctival fibroblasts is modulated by FGF-2 and substratum stiffness.
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DOI：
10.1371/journal.pone.0242626
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发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Inoue T
中科院分区：
文献类型：
--
作者：
Matsumura T;Fujimoto T;Futakuchi A;Takihara Y;Watanabe-Kitamura F;Takahashi E;Inoue-Mochita M;Tanihara H;Inoue T
本研究旨在探讨基质硬度对人结膜成纤维细胞对转化生长因子（TGF）-β敏感性的影响，并探讨其作用的分子机制。人结膜成纤维细胞在胶原蛋白包被的塑料或硅胶板上培养。硅胶板的刚度为 0.2 或 64 kPa。用 2.5 ng/mL TGF-β2（含或不含成纤维细胞生长因子 (FGF)-2 (0–100 ng/mL)）处理细胞 24 小时或 48 小时。通过蛋白质印迹分析测定蛋白质表达水平。使用 WST-8 测定评估细胞增殖。 FGF-2 抑制 TGF-β 诱导的 α-平滑肌肌动蛋白 (SMA) 和 I 型胶原蛋白 (Col I) 的表达，但不抑制纤连蛋白 (FN)。 FGF-2 和 TGF-β2 均能增加细胞增殖，但没有相加效应。 TGF-β2 对 α-SMA 的诱导在软基质上减少，而 Yes 相关蛋白/具有 PDZ 结合基序的转录共激活因子 (YAP/TAZ) 的表达水平或亚细胞位置没有任何变化。即使在软基质上，FGF-2 也能抑制 TGF-β 诱导的 α-SMA 表达。 FGF-2 处理和软基质抑制了 TGF-β 诱导的结膜成纤维细胞向肌成纤维细胞的转分化。 FGF-2 减弱了 TGF-β 诱导的 α-SMA 表达，即使在柔软的基质上也是如此。
This study aimed to investigate the effects of substratum stiffness on the sensitivity of human conjunctival fibroblasts to transforming growth factor (TGF)-β, and to explore the molecular mechanism of action. Human conjunctival fibroblasts were cultured on collagen-coated plastic or silicone plates. The stiffness of the silicone plates was 0.2 or 64 kPa. Cells were treated by 2.5 ng/mL TGF-β2 with or without fibroblast growth factor (FGF)-2 (0–100 ng/mL) for 24 h or 48 h. The protein expression levels were determined by Western blot analysis. Cell proliferation was assessed using the WST-8 assay. FGF-2 suppressed the TGF-β-induced expression of α-smooth muscle actin (SMA) and collagen type I (Col I), but not fibronectin (FN). Both FGF-2 and TGF-β2 increased cell proliferation without an additive effect. The induction of α-SMA by TGF-β2 was decreased on the soft substratum, without any change in the expression level or subcellular location of Yes-associated protein/transcriptional coactivator with PDZ-binding motif (YAP/TAZ). FGF-2 suppressed TGF-β-induced α-SMA expression even on the soft substratum. FGF-2 treatment and a soft substratum suppressed TGF-β-induced transdifferentiation of conjunctival fibroblasts into myofibroblasts. FGF-2 attenuated the TGF-β-induced expression of α-SMA, even on a soft substratum.
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影响因子：
10.5
作者：
Meng Z;Moroishi T;Guan KL
通讯作者：
Guan KL
影响因子：
64.5
作者：
Rosenbluh J;Nijhawan D;Cox AG;Li X;Neal JT;Schafer EJ;Zack TI;Wang X;Tsherniak A;Schinzel AC;Shao DD;Schumacher SE;Weir BA;Vazquez F;Cowley GS;Root DE;Mesirov JP;Beroukhim R;Kuo CJ;Goessling W;Hahn WC
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6.2
作者：
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通讯作者：
Hughes-Fulford, Millie
影响因子：
3.7
作者：
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通讯作者：
Migdal, C S
影响因子：
20.1
作者：
Cheng, GC;Briggs, WH;Lee, RT
通讯作者：
Lee, RT