特發性肺纖維化（IPF）是嚴重且致命的肺纖維化疾病，但此疾病的造成主因仍然未知。疤痕組織在肺內生長使IPF患者的肺組織變得堅硬而失去彈性。受損的器官所釋放的發炎性物質會刺激纖維母細胞(fibroblasts)活化與增殖成肌纖維母細胞(myofibroblasts)。而其中，pentraxin-3 (PTX3)在組織重塑中扮演著重要的角色並且參與在發炎中。在受到外來物的感染刺激時，PTX3在血液中的濃度會快速增加。因此， PTX3是否參與並且調節肺纖維化的相關特性成為本研究的主要課題。實驗結果顯示，在博萊黴素(bleomycin)誘導的肺纖維化小鼠模式中，博來黴素可以誘導PTX3的表現。在小鼠與人類的纖維母細胞中，PTX3會誘導肺纖維化相關蛋白包括纖連蛋白(fibronectin)、第一型膠原蛋白(collagen type I)與平滑肌肌動蛋白(α-SMA)的表現。雖然PTX3無法促進細胞的增殖，但能刺激細胞的遷移及膠原蛋白的累積。進一步實驗結果發現PTX3可以誘導β-catenin，NF-κB，JNK與c-Jun的磷酸化。最後，利用PTX3抑制劑來評估其在肺纖維化中的功效，結果證實PTX3抑制劑可以抑制PTX3所誘導的肺纖維母細胞的活化。綜合以上所述，本研究首次證明PTX3參與在組織纖維化進程，並且我們實驗室所開發出的PTX3抑制劑在未來也許能為IPF治療帶來新曙光。

Idiopathic pulmonary fibrosis (IPF) is a serious and fatal lung fibrosis disease of which the major causes remain unknown. Scar tissue grows inside of lungs and makes the lung tissue thicker and stiffer in IPF. The release of inflammatory mediators by the injured organ can stimulate the proliferation of myofibroblasts which are derived by the activation of fibroblasts. Pentraxin-3 (PTX3) plays a role in tissue remodeling and is involved in inflammation. PTX3 is increased rapidly in blood level during infectious conditions. This study investigated whether PTX3 is involved and regulate the features of pulmonary fibrosis. As the results, in bleomycin-induced pulmonary fibrosis mice model, the expression of PTX3 was increased in lung tissue. In addition, PTX3 induced the expression of lung fibrosis-related proteins in mice and human lung fibroblasts. Though PTX3 has no effect on the proliferation of lung fibroblasts, cell migration was increased following the treatment of PTX3. Also, PTX3 stimulated the collagen accumulation. Further, PTX3 could induce the phosphorylation of β-catenin, NF-κB, JNK and c-Jun. Finally, PTX3 inhibitors could attenuate the fibroblast activation in vitro. Taken together, this study first demonstrated that PTX3 is involved in fibrosis in vitro and in vivo. The established PTX3 inhibitors provide a great opportunity for applying to IPF therapy in the future.

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