Thy1 (CD90) Expression Is Elevated in Radiation-Induced Periprosthetic Capsular Contracture: Implication for Novel Therapeutics.
Thy1 (CD90) Expression Is Elevated in Radiation-Induced Periprosthetic Capsular Contracture: Implication for Novel Therapeutics.
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DOI：
10.1097/prs.0000000000003542
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发表时间：
2017-08
影响因子：
3.6
通讯作者：
Phipps RP
中科院分区：
文献类型：
--
作者：
Hansen TC;Woeller CF;Lacy SH;Koltz PF;Langstein HN;Phipps RP
乳房包膜挛缩是乳房切除术后假体乳房重建术的致命并发症。不幸的是，乳房包膜挛缩率急剧增加的靶向放疗，标准后乳房切除术治疗。Thy1（也称为CD90）在肌成纤维细胞分化和瘢痕组织形成中起重要作用。然而，放疗对Thy1表达的影响以及Thy1在包膜挛缩中的作用尚不清楚。我们通过RT-qPCR、Western blotting和免疫组织化学分析了Thy1在原代人包膜组织和原代成纤维细胞外植体中的表达。使用RNA干扰来去除Thy1，以确定在包膜成纤维细胞中，Thy1的表达是否对肌成纤维细胞表型至关重要。此外，我们用一种新的抗瘢痕化合物盐霉素处理人荚膜成纤维细胞，以确定盐霉素是否能阻断Thy1的表达和肌成纤维细胞的形成。在此，我们发现放射治疗显著增加了种植体周围瘢痕组织中Thy1 mRNA和蛋白的表达。瘢痕组织外植的荚膜成纤维细胞保留了使肌成纤维细胞产生瘢痕形成成分胶原I和α-平滑肌肌动蛋白（αSMA）的能力。Thy1的缺失降低了囊成纤维细胞的纤维化形态，显著降低了αSMA和胶原蛋白的水平。此外，我们首次发现盐霉素降低了Thy1的表达，并阻止了包膜成纤维细胞中肌成纤维细胞的形成。这些数据表明，电离辐射诱导的Thy1过表达可能会增加包膜挛缩的严重程度，并且可以通过靶向Thy1表达来改善成纤维细胞疤痕的产生。重要的是，我们的新结果显示了盐霉素在辐射诱导的包膜挛缩中的抗疤痕能力。
Capsular contracture is a devastating complication of post-mastectomy implant-based breast reconstruction. Unfortunately, capsular contracture rates are drastically increased by targeted radiotherapy, a standard post-mastectomy treatment. Thy1 (also called CD90) is important in myofibroblast differentiation and scar tissue formation. However, the impact of radiotherapy on Thy1 expression and the role of Thy1 in capsular contracture are unknown. We analyzed Thy1 expression in primary human capsular tissue and primary fibroblast explants by RT-qPCR, Western blotting, and immunohistochemistry. Thy1 was depleted using RNA interference to determine if Thy1 expression was essential for the myofibroblast phenotype in capsular fibroblasts. Furthermore, human capsular fibroblasts were treated with a new anti-scarring compound, salinomycin to determine if Thy1 expression and myofibroblast formation were blocked by salinomycin. Herein, we show that radiation therapy significantly increased Thy1 mRNA and protein expression in peri-implant scar tissue. Capsular fibroblasts explanted from scar tissue retained the ability to make the myofibroblast produced scar forming components collagen I and α-smooth muscle actin (αSMA). Depletion of Thy1 decreased the fibrotic morphology of capsular fibroblasts and significantly decreased αSMA and collagen levels. Furthermore, we show for the first time that salinomycin decreased Thy1 expression and prevented myofibroblast formation in capsular fibroblasts. These data reveal that ionizing radiation-induced Thy1 over-expression may contribute to increased capsular contracture severity, and fibroblast scar production can be ameliorated through targeting Thy1 expression. Importantly, our new results show promise for the anti-scarring ability of salinomycin in radiation-induced capsular contracture.