蟹足腫 (Keloid) 是一種伴隨慢性發炎的纖維化疾病，它的特徵在於細胞外基質 (ECM) 過度增生並沉積，能夠超出原始傷口的邊界侵犯正常皮膚。在蟹足腫中的角質細胞已經被證實具有上皮-間質轉化 (EMT) 的現象，進而導致角質細胞出現黏附異常以及遷移增加，顯示出角質細胞的異常可能影響蟹足腫的進程。然而，參與蟹足腫發展過程中關鍵且有效的促發炎因子仍有許多不清楚，因此剖析及應用它們的參與及開發用於治療蟹足腫的有用藥物仍是有待解決的問題。聚環蛋白3 (PTX3) 是已知的發炎相關因子，它有助於許多慢性發炎的疾病的發生，像是纖維化。在本篇研究中發現聚環蛋白3會大量的表現在蟹足腫患者的角質細胞中。本篇研究數據證明腫瘤壞死因子-α (TNF-α)會刺激活化角質細胞中的轉錄因子CCAAT /增強子結合蛋白 (CEBPD)增加，進而強化聚環蛋白3基因轉錄活性。並且，聚環蛋白3在角質細胞中會透過CD44誘導上皮-間質轉化作用，進而參與角質細胞纖維化和細胞遷移。進一步在透過加入聚環蛋白3抑制劑及降低CD44表達的實驗中，發現由聚環蛋白3所誘導的上皮-間質轉化作、纖維化和細胞遷移均受到抑制。因此，本篇研究確定聚環蛋白3在蟹足腫角質細胞內的參與，並且支持聚環蛋白3抑制劑可作為未來蟹足腫治療的潛力藥物。

Keloid is an inflammation-associated fibrotic disease, which is caused by abnormal extracellular matrix deposition during the wound healing of damaged skin. It shows excess cell migration and proliferation that leads to extended cell increase of the original wound. Recently, several studies reported that dysregulated responses of keratinocytes are occurred by the epithelial-mesenchymal transition (EMT), which suggests abnormal differentiation and adhesion of keratinocytes associate with keloid progression. However, the details including identifying critical and effective inflammatory factors during keloid progression are still uncertain. The dissection of the involvement and develop useful drugs for the inhibition of keloid remains an open question. Pentraxin 3 (PTX3), a pro-inflammatory factor, plays an important role in innate immunity, inflammation, and fibrosis. In a previous study, PTX3-mediated effect was indicated to involve in cell migration and invasion. It was found that high PTX3 expression was observed in keloid patients and accumulated in keratinocytes. The data showed that tumor necrosis factor-alpha (TNF-α) induced the expression of CCAAT/enhancer binding protein (CEBPD) and PTX3 in HaCaT cells. It means that CEBPD and PTX3 were increased in keratinocytes in an inflammatory environment. In addition, PTX3 induces the EMT process, activation of EMT markers, such as vimentin, twist, snail and alpha-smooth muscle actin (α-SMA), and the ability of cell migration through CD44 in HaCaT cells. HaCaT cells were tend to differentiation toward fibroblasts/myofibroblasts-like cells through EMT process, and further enhance collagen deposition and increased the fibrosis-related markers, including fibronectin, collagen type I and collagen type III. PTX3 also participated in keloid progression by affecting HaCaT cells. Thus, the PTX3 inhibitor was used to inhibit the effects that caused by PTX3. The data showed that the PTX3 inhibitor can inhibit cell fibrosis and migration by suppressing the EMT process in HaCaT cells. This study suggested that the functional role of PTX3 and provides a targetable therapy for keloid.

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