Platelet-Rich Plasma Prevents In Vitro Transforming Growth Factor-β1-Induced Fibroblast to Myofibroblast Transition: Involvement of Vascular Endothelial Growth Factor (VEGF)-A/VEGF Receptor-1-Mediated Signaling (†).
Platelet-Rich Plasma Prevents In Vitro Transforming Growth Factor-β1-Induced Fibroblast to Myofibroblast Transition: Involvement of Vascular Endothelial Growth Factor (VEGF)-A/VEGF Receptor-1-Mediated Signaling (†).
复制标题
富血小板血浆在体外阻止转化生长因子-β1诱导的成纤维细胞向肌成纤维细胞转化：血管内皮生长因子（VEGF）-A/VEGF受体-1介导的信号转导（†）。
DOI：
10.3390/cells7090142
复制
发表时间：
2018-09-19
期刊：
影响因子：
6
通讯作者：
Sassoli C
中科院分区：
文献类型：
--
作者：
Chellini F;Tani A;Vallone L;Nosi D;Pavan P;Bambi F;Zecchi Orlandini S;Sassoli C
富血小板血浆（PRP）的抗纤维化潜力存在争议。本研究检查了PRP对体外转化生长因子（TGF）-β1诱导的成纤维细胞分化为肌成纤维细胞（纤维化的主要驱动因素）的影响，以及血管内皮生长因子（VEGF）-A介导PRP诱导的反应。还评估了单独PRP对成纤维细胞分化的影响。通过共聚焦荧光显微镜和蛋白质印迹分析α-平滑肌肌动蛋白（sma）和1型胶原蛋白的表达、粘着斑聚集和应力纤维组装来评估肌成纤维细胞的表型。Notch-1、连接蛋白43和VEGF-A的表达也通过RT-PCR分析。富血小板血浆通过VEGF-A/VEGF受体（VEGFR）-1介导的对TGF-β1/Smad 3信号传导的抑制来负向调节成纤维细胞-肌成纤维细胞的转变。事实上，TGF-β1/PRP共处理的成纤维细胞显示出肌纤维母细胞表型的稳健衰减，伴随着Smad 3表达水平的降低。通过KRN 633或阻断抗体的VEGFR-1抑制，或这些细胞中的VEGF-A中和，阻止了PRP促进的作用。PRP还能抑制TGF-β1诱导的VEGF-A和VEGFR-1表达的降低。通过用可溶性VEGF-A处理细胞证实了VEGF-A信号传导在抵消肌成纤维细胞生成中的作用。PRP作为单一处理不诱导成纤维细胞肌分化。这项研究为PRP抗纤维化作用的细胞和分子机制提供了新的见解。
The antifibrotic potential of platelet-rich plasma (PRP) is controversial. This study examined the effects of PRP on in vitro transforming growth factor (TGF)-β1-induced differentiation of fibroblasts into myofibroblasts, the main drivers of fibrosis, and the involvement of vascular endothelial growth factor (VEGF)-A in mediating PRP-induced responses. The impact of PRP alone on fibroblast differentiation was also assessed. Myofibroblastic phenotype was evaluated by confocal fluorescence microscopy and western blotting analyses of α-smooth muscle actin (sma) and type-1 collagen expression, vinculin-rich focal adhesion clustering, and stress fiber assembly. Notch-1, connexin 43, and VEGF-A expression were also analyzed by RT-PCR. PRP negatively regulated fibroblast-myofibroblast transition via VEGF-A/VEGF receptor (VEGFR)-1-mediated inhibition of TGF-β1/Smad3 signaling. Indeed TGF-β1/PRP co-treated fibroblasts showed a robust attenuation of the myofibroblastic phenotype concomitant with a decrease of Smad3 expression levels. The VEGFR-1 inhibition by KRN633 or blocking antibodies, or VEGF-A neutralization in these cells prevented the PRP-promoted effects. Moreover PRP abrogated the TGF-β1-induced reduction of VEGF-A and VEGFR-1 cell expression. The role of VEGF-A signaling in counteracting myofibroblast generation was confirmed by cell treatment with soluble VEGF-A. PRP as single treatment did not induce fibroblast myodifferentiation. This study provides new insights into cellular and molecular mechanisms underpinning PRP antifibrotic action.
登录
查看更多内容
影响因子：
4.3
作者：
Caceres, Monica;Martinez, Constanza;Smith, Patricio C.
通讯作者：
Smith, Patricio C.
影响因子：
4.8
作者：
Delos, Demetris;Leineweber, Matthew J.;Rodeo, Scott Alan
通讯作者：
Rodeo, Scott Alan
影响因子：
3
作者：
Duan, Xuejing;Ji, Mei;Lin, Zhiyong
通讯作者：
Lin, Zhiyong
DOI：
10.4103/jomfp.jomfp_146_15
发表时间：
2017-09-01
期刊：
Journal of oral and maxillofacial pathology : JOMFP
影响因子：
--
作者：
Bagalad, Bhavana S;Mohan Kumar, K P;Puneeth, H K
通讯作者：
Puneeth, H K
影响因子：
5.6
作者：
Caja L;Dituri F;Mancarella S;Caballero-Diaz D;Moustakas A;Giannelli G;Fabregat I
通讯作者：
Fabregat I