我國人民罹患肝臟疾病者眾，長期以來肝病死亡率居高不下。Huang等人在2004年發現在肝臟膽道閉鎖的過程中，DLK1基因會顯著的減少。現今對於DLK1參與的作用機制尚不清楚，因此本研究想要探討DLK1蛋白對肝臟細胞在傷口癒合相關功能的影響。本研究首先假設DLK1可能參與: (1) 肝組織再生; (2)肝臟星狀細胞活化的過程。
本研究生產出具有功能的DLK1蛋白細胞外EGF-like序列片段，以細胞培養的方式測試肝臟組織再生的生物特性。結果顯示，添加DLK1蛋白至本研究的細胞培養系統，在DLK1濃度4~8ng/ml可促進肝臟主要的上皮細胞的增生與移行，表示DLK1可以促進肝臟主要細胞的補充。添加DLK1蛋白在濃度0.01~1μg/ml可促進內皮細胞與纖維母細胞的增生及移行，顯示DLK1可能具有促進血管新生的作用，更加證明了DLK1可能具有促進肝組織再生的功能。
本研究成功分離培養鼠肝星狀細胞，外加DLK1於星狀細胞的細胞培養系統中，結果顯示，在DLK1濃度0.01~1μg/ml，可促進初期星狀細胞增生、移行的能力；相反地，DLK1抑制已活化星狀細胞的增生、移行及表現smooth muscle α-actin等活化特性的能力。過去研究指出，當肝臟受到傷害，星狀細胞的活化為傷口修復的關鍵過程，但星狀細胞持續的活化為造成肝纖維化的主要原因。推論DLK1可能具有幫助肝臟傷口癒合及抑制肝臟星狀的過度活化的功能。
肝臟疾病一直是台灣人的國病，本研究依實驗結果提出一假設，「DLK1可能具有促進肝組織再生及抑制肝纖維化的作用」，可望進一步的研究，深入瞭解DLK在體內的生物功能與機制。

Liver disease is a severe problem in Taiwan. Recently Huang et al. reported that Delta-like protein (DLK1) was demonstrated to decrease significantly in the progression of liver fibrosis in biliary atresia. It is suggested that DLK1 maybe involve in the pathogenesis of liver fibrosis. However, the molecular mechanism underlying the implication is still unknown. This study was aimed to investigate effects of DLK1 on liver cells during wound healing .We hypothesize that DLK1 maybe involve in the progression of liver injury by promoting liver regeneration and affecting activation of HSCs.
In liver regeneration, we produced recombinant DLK1 protein containing the extracellular domain of human DLK1 (DLK-EC). The results show that DLK-EC can promote proliferation and migration of hepatocytes, the major liver cells. It is suggested DLK-EC can promote hepatocyte recruitment. Adding DLK-EC to the culture medium can promote proliferation and migration of endothelial cells and fibroblasts. These results support that DLK-EC has functions during liver regeneration.
In activation of HSCs, we added recombinant DLK-EC protein into HSCs cell culture. Experimental results show DLK-EC promotes proliferation and migration of freshly isolated HSCs and inhibits the proliferation, migration and smooth muscle α-actin expression of perpetual activated HSCs.
The results of the study support that DLK1 is implicated with liver regeneration and inhibition of fibrogenesis.

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