分泌性蛋白Lcn2對初級小鼠子宮內膜上皮細胞生理機制的影響

Lcn2是疏水性分子結合蛋白家族中的一員，在哺乳類的系統中屬於分泌性蛋白，可做自泌或旁泌的生理反應，已知Lcn2為一種急性反應蛋白(actue phase protein)，在細胞受到多種不同環境壓力時會被誘導分泌。由於在細胞遭受環境壓力時可能會由表皮細胞轉換成間質細胞(Epithelial-mesenchymal transition, EMT)的現象，許多文獻也指出Lcn2與EMT之間可能有互動關係。為了解Lcn2是否參與在生殖系統中EMT過程，因此根據Glasser等人的方法，建立初級培養小鼠子宮內膜上皮細胞培養系統，並以cytokeratin抗體鑑定之。採用長時間營養缺乏的環境壓力培養條件來誘導Lcn2蛋白的產生，探討Lcn2是否會使小鼠子宮內膜上皮細胞發生EMT，以及誘發EMT對子宮內膜上皮細胞的生理現象是否造成影響。實驗結果顯示在環境的壓力下可以誘導初級小鼠子宮內膜上皮細胞表現Lcn2蛋白，且Lcn2蛋白可以促進初級小鼠子宮內膜上皮細胞轉化成間質細胞，造成上皮細胞標誌-細胞角蛋白(cytokeratin)表現量減少，間質細胞標誌-纖維連接蛋白(fibronectin)表現量增加，導致細胞由聚集狀態轉變為紡錘狀及分散分布，此一變化可能會增加細胞的移動能力和侵襲能力，推測Lcn2可能參與子宮內膜病變的生成。

關鍵字

Lcn2 ；小鼠子宮內膜上皮細胞；表皮細胞轉換至間質細胞；細胞角蛋白；纖維連接蛋白

並列摘要

Lcn2, a member of the lipocalin family, is as a secretory protein in mammalian system as well as has autocrine and paracrine physical functions. A well known, Lcn2 is an acute phase protein and is induced by stress conditions in cells. Owing to the stress, epithelial to mesenchymal transition (EMT) could occur and the substantial evidences encourage us to figure out the relationship between Lcn2 and EMT in primary endometrial epithelium cell. To establish primary culture system of mouse endometrial epithelium cell is our matter of immediate urgency. According to the method of Glasser et al, after trypsin digestion, we haversted primary endometrial epithelium cells and the cells have been identified with cytokeratin antibody. Using nutrition deprivation as a stress condition, we could induce highly Lcn2 expression in this endometrial epithelium cell. To elucidate whether Lcn2 triggers the EMT in endometrial epithelium cell then initiates the influence of the cell function in reproductive system is our goal. As the Lcn2 expression in high level, the cell morphology would change from round-up to spindle-like then the cell dispersion would happen. Meanwhile, double immunostaining showed cytokeratin expression was diminished and fibronectin expression was increased, and an additive effects on cell migration and cell invasion. These results demonstrate that Lcn2 could be induced by environmental stress and trigger the EMT in primary mouse endometrial epithelium cell. These data shield some light on the participation of Lcn2 in the pathologies of endometrial system.

並列關鍵字

Lcn2 ； mouse endometrial epithelium ； epithelial to mesenchymal transition (EMT) ； cytokeratin ； fibronectin

參考文獻

Ackland ML et al., Epidermal growth factor-induced epithelio-mesenchymal transition in human breast carcinoma cells. Lab Invest. 2003;83(3):435-48.

Barberà MJ, Puig I, Domínguez D et al., Regulation of Snail transcription during epithelial to mesenchymal transition of tumor cells. Oncogene. 2004; 23(44): 7345-54.

Becker KF, Rosivatz E et al., Analysis of the E-cadherin repressor Snail in primary human cancers. Cells Tissues Organs. 2007; 185(1-3): 204-12.

Bellovin DI, Simpson KJ et al., Reciprocal regulation of RhoA and RhoC characterizes the EMT and identifies RhoC as a prognostic marker of colon carcinoma. Oncogene. 2006; 25(52):6959-67.

Berger T, Togawa A, Duncan GS, Elia AJ, You-Ten A, Wakeham A, et al. Lipocalin 2-deficient mice exhibit increased sensitivity to Escherichia coli infection but not to ischemia-reperfusion injury. Proc Natl Acad Sci USA 2006; 103:1834-9.

國際替代計量

分泌性蛋白Lcn2對初級小鼠子宮內膜上皮細胞生理機制的影響

全文下載

主題瀏覽