上皮間質轉化(Epithelial-mesenchymal transition, EMT)，是一種細胞成長發育受到發炎相關作用時上皮細胞分化的一個重要機制。近期研究顯示，逆轉上皮間質轉化與逆轉腎臟纖維化相關，但其中的分子機制仍未清楚。Pentraxin 3（PTX3）已被證實在傷口癒合時的炎症和組織重建中發揮關鍵作用，另外在腎纖維化中也觀察到PTX3 增加，但是PTX3 和腎臟上皮間質轉化之間詳細的分子機制仍是個懸而未解的問題。此研究針對腎臟上皮細胞(HK2), 除探討 PTX3 活化抗細胞凋亡分子Mcl-1，還觀察出PTX3誘導上皮間質轉化之相關基因Snail, Twist1/2，以及乙型轉化生長因子和細胞外基質蛋白α-SMA, Vimentin and Collagen I 之表現。結果顯示PTX3有助於上皮間質轉化和抗凋亡並增加細胞外基質，另外PTX3還誘導乙型轉化生長因子轉錄活化蛋白LTBP-1。最後，利用PTX3 抑制劑可抑制LTBP-1 轉錄和上述細胞外基質蛋白表現，本研究顯示除了PTX3抑制劑應用於臨床治療外，也說明PTX3可以成為腎臟纖維化進展標誌基因之可能。

Development of renal fibrosis has been recognized as common outcome of chronic kidney disease (CKD) by relentless inflammatory response and fibrotic progression in tumorigenesis in which epithelial-mesenchymal transition (EMT) is as a convergence point. Consequently, dissecting regulatory mechanism in controlling activation and development of EMT during renal fibrosis is necessary for finding a good marker for early diagnostic and developing effective therapeutic interventions to help for reducing mortality rate every year. Pentraxin 3 (PTX3) has been suggested to play a key role in inflammation and tissue remodeling process during wound healing. Interestingly, increased PTX3 was also observed in renal fibrosis. However, the detailed regulation between PTX3 and renal EMT remains an open question. In this study, in addition to activating anti-apoptotic protein Mcl-1 expression, PTX3 induces EMT markers, including Snail, Twist1/2 transcripts, -SMA, Vimentin and pro-fibrotic protein Collagen type I in HK2 cells. Of note, PTX3 is in positive correlation with TGF-b1. The results imply that PTX3 contributes to EMT and anti-apoptosis and increased extracellular matrix (ECM). Moreover, PTX3 further activated latent TGF-b binding protein 1 (LTBP-1) transcription. However, PTX3 inhibitors can suppress LTBP-1 transcription and expression of EMT makers. Together, results of this study implicates a new therapeutic strategy as well as potential marker for detecting early renal fibrosis.

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