Yang Ying, Li Shumo, Bian Li, Dai Xiaoming, Hu Jun, Ma Yun, Wang Zhiyuan
Department of Pathology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
Department of Breast Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
Sci Rep. 2025 Jul 15;15(1):25649. doi: 10.1038/s41598-025-11409-9.
Capsular contraction is the most common complication after breast augmentation or reconstruction, and is the main reason underlying patient dissatisfaction and additional subsequent surgeries. Periostin is an extracellular matrix protein and a member of TGF-β superfamily. Studies have shown that periostin is closely related to fibrosis, collagen cross-linking and tissue remodeling. In this study, we observed the expression of periostin and other fibrosis-related proteins in the capsule of human breast silicon implant, assessing their relationship with the extent of capsule fibrosis. By using human breast derived fibroblasts with manipulated periostin expression level, we explored periostin's impact on other fibrosis-related cytokines, fibroblast proliferation, differentiation, and collagen synthesis. Furthermore, we employed a murine model of prosthesis implantation to elucidate the roles of periostin and lysyl oxidase (LOX) in capsule formation. Immunohistochemical analysis of clinical capsular specimens revealed a significant correlation between periostin expression levels and the severity of capsular contracture. In vitro experiments using human breast-derived fibroblasts demonstrated that periostin promotes fibroblast proliferation and regulates the expression of key fibrosis-related proteins such as LOX, BMP-1, fibronectin, and tenascin-C at both protein and mRNA levels. Moreover, periostin was found to induce fibroblast differentiation into myofibroblasts and enhance collagen production. In the murine model of prosthesis implantation, periostin and LOX were observed to increase the thickness of the prosthesis capsule, whereas the administration of the LOX inhibitor β-aminopropionitrile (BAPN) significantly attenuated capsule formation. Our study underscores the significant role of periostin in the pathogenesis of breast prosthesis capsule formation and contracture. These findings provide novel insights into the mechanisms underlying capsular contracture and suggest periostin as a potential therapeutic target for mitigating this complication.
包膜挛缩是隆胸或乳房重建术后最常见的并发症，也是患者不满以及后续额外手术的主要原因。骨膜蛋白是一种细胞外基质蛋白，属于转化生长因子-β超家族成员。研究表明，骨膜蛋白与纤维化、胶原交联和组织重塑密切相关。在本研究中，我们观察了人乳房硅胶植入物包膜中骨膜蛋白及其他纤维化相关蛋白的表达，评估它们与包膜纤维化程度的关系。通过使用骨膜蛋白表达水平被操控的人乳腺来源的成纤维细胞，我们探究了骨膜蛋白对其他纤维化相关细胞因子、成纤维细胞增殖、分化及胶原合成的影响。此外，我们采用假体植入的小鼠模型来阐明骨膜蛋白和赖氨酰氧化酶（LOX）在包膜形成中的作用。对临床包膜标本的免疫组织化学分析显示，骨膜蛋白表达水平与包膜挛缩的严重程度之间存在显著相关性。使用人乳腺来源的成纤维细胞进行的体外实验表明，骨膜蛋白在蛋白质和mRNA水平上均促进成纤维细胞增殖，并调节关键纤维化相关蛋白如LOX、骨形态发生蛋白-1（BMP-1）、纤连蛋白和肌腱蛋白-C的表达。此外，发现骨膜蛋白可诱导成纤维细胞分化为肌成纤维细胞并增强胶原生成。在假体植入的小鼠模型中，观察到骨膜蛋白和LOX可增加假体包膜厚度，而给予LOX抑制剂β-氨基丙腈（BAPN）可显著减轻包膜形成。我们的研究强调了骨膜蛋白在乳房假体包膜形成和挛缩发病机制中的重要作用。这些发现为包膜挛缩的潜在机制提供了新的见解，并表明骨膜蛋白作为减轻这种并发症的潜在治疗靶点。
