Abstract
Although the research on the localization of trachea stem cells has made a rapid progress, the mechanism of proliferation and differentiation of trachea stem cells remains unclear. The objective of this study is to observe and analyze the recovery process of mice tracheal epithelium injured by 5-FU, and to investigate the mechanism involved in the regulation of tracheal stem cells proliferation and differentiation through morphological, immunofluorescence, and microarray analysis. After treatment with 5-FU, the mature cells were dead and desquamated. Only a few G0 phase cells remained on the basement membrane. When supplied with normal culture media, the cells eventually became flat, cubic, and restored as pseudostratified epithelium. These G0 phase cells were ABCG2 positive. It suggested that these cells could differentiate into cilia cells or Clara cells, and had the multi-differentiation ability of stem cells. We examinated the expression profile of genes involved in the stem cell differentiation in normal tracheal epithelial cells and the regenerated epithelial cells at 24 and 48 h after injured by 5-FU using gene microarray. After 24 h treatment, 8 genes were up-regulated and 31 genes were down-regulated. After 48 h treatment, 5 genes were up-regulated and 42 genes were down-regulated. The differential gene expressions in gene microarray analysis focused on cell cycle regulation, intercellular junction, fibroblast growth factors, bone morphogenetic protein, Notch and Wnt-signaling pathways, which suggested that the differential gene expressions might be closely associated with the proliferation and differentiation of tracheal stem cells.
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Jia, X. S., Hasui, K., et al. (2003). Observation of rat tracheal stem cells during the injure and regeneration induced by 5-FU. Proceedings of the Japanese Society Pathology, 92, 327.
Ding, Q., Jia, X. S., & Zhou, Y. (2004). Study of tracheal regeneration after injury induced by 5-fluorouracil in rats. Zhonghua Bing Li Xue Za Zhi, 33, 143–145.
Ding, Q., & Jia, X. S. (2004). Observation of rat tracheal stem cells during the injure and regeneration induced by 5-FU. Acta Anatomica Sinica, 35, 328–330.
Zhou, Y., Jia, X. S., & Ding, Q. (2003). Study of human bronchia epithelium injury induced by fluorouracil and on location of bronchial stem cells. Chinese Journal of Histochemistry and Cytochemistry, 12, 286–290.
Wang, L. L., & Jia, X. S. (2006). Expression of ABCG2 transporter during tracheal regeneration in rats. Acta Anatomica Sinica, 34, 186–190.
Jia, X. S., Hasui, K., et al. (2006). Stem cell proliferation, differentiation process of the trachea Wnt pathways. Proceedings of the Japanese Society Pathology, 95, 294.
Dahlqvist, C., Blokzijl, A., Chapman, G., et al. (2003). Functional Notch signaling is required for BMP4-induced inhibition of myogenic differentiation. Development, 130, 6089–6099.
Reya, T., & Clevers, H. (2005). Wnt signalling in stem cells and cancer. Nature, 434, 843–850.
Lv, W. L., & Jia, X. S. (2006). Expression of Wnt-1 in rat tracheal stem cell during the early proliferation and differentiation. Acta Anatomica Sinica, 34, 192–194.
Ma, X. B., Jia, X. S., Liu, Y. L., Wang, L. L., Sun, S. L., Song, N., et al. (2009). Expression and role of Notch signaling in the regeneration of rat tracheal epithelium. Cell proliferation, 42, 15–28.
Acknowledgment
This work was supported by Grants from the National Natural Science Funds (to JIA Xinshan) (No. 30170407).
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Zhang, JR., Song, N., Jia, XS. et al. The Recovery Process of Mice Tracheal Epithelium Injured by 5-FU and Its Microarray Analysis. Cell Biochem Biophys 70, 1691–1697 (2014). https://doi.org/10.1007/s12013-014-0115-1
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DOI: https://doi.org/10.1007/s12013-014-0115-1