Aortic Valve Endothelial Cells Undergo Transforming Growth Factor-β-Mediated and Non-Transforming Growth Factor-β-Mediated Transdifferentiation in Vitro

作者: Gretchen Paranya , Sabrina Vineberg , Evan Dvorin , Sunjay Kaushal , Stephen J. Roth

DOI: 10.1016/S0002-9440(10)62520-5

关键词: CD31EndotheliumEndothelial stem cellCellular differentiationCell biologyCell TransdifferentiationTransforming growth factor betaPathologyTransforming growth factorBiologyTransdifferentiation

摘要: Cardiac valves arise from endocardial cushions, specialized regions of the developing heart that are formed by an endothelial-to-mesenchymal cell transdifferentiation. Whether and to what extent this transdifferentiation is retained in mature unknown. Herein we show endothelial cells can transdifferentiate a mesenchymal phenotype. Using induction α-smooth muscle actin (α-SMA), established marker for process, two distinct pathways were identified clonally derived populations isolated ovine aortic valve leaflets. α-SMA expression was induced culturing clonal medium containing either transforming growth factor-β or low levels serum no basic fibroblast factor. Cells express exhibited markedly increased migration response platelet-derived factor-BB, consistent with A population differentiated co-expressed CD31, marker, along α-SMA, as seen double-label immunofluorescence. Similarly, co-expression markers detected subpopulation frozen sections valves, suggesting may occur vivo. Hence, valvular described here provide powerful vitro model dissecting molecular events regulate endothelium.

参考文章(31)
A I Gotlieb, D L Mulholland, Cell biology of valvular interstitial cells. Canadian Journal of Cardiology. ,vol. 12, pp. 231- 236 ,(1996)
Ana M. Schor, Seth L. Schor, Enrique Arciniegas, 6 – Phenotypic diversity and lineage relationships in vascular endothelial cells Stem Cells. pp. 119- 146 ,(1997) , 10.1016/B978-012563455-7/50007-6
V. Moulin, D. Garrel, F. A. Auger, M. O’Connor-McCourt, G. Castilloux, L. Germain, What's new in human wound-healing myofibroblasts? Current topics in pathology. Ergebnisse der Pathologie. ,vol. 93, pp. 123- 133 ,(1999) , 10.1007/978-3-642-58456-5_13
Ann M. Ranger, Michael J. Grusby, Martin R. Hodge, Ellen M. Gravallese, Fabienne Charles de la Brousse, Tim Hoey, Craig Mickanin, H. Scott Baldwin, Laurie H. Glimcher, The transcription factor NF-ATc is essential for cardiac valve formation Nature. ,vol. 392, pp. 186- 190 ,(1998) , 10.1038/32426
José Luis de la Pompa, Luika A. Timmerman, Hiroaki Takimoto, Hiroki Yoshida, Andrew J. Elia, Enrique Samper, Julia Potter, Andrew Wakeham, Luc Marengere, B. Lowell Langille, Gerald R. Crabtree, Tak W. Mak, Role of the NF-ATc transcription factor in morphogenesis of cardiac valves and septum Nature. ,vol. 392, pp. 182- 186 ,(1998) , 10.1038/32419
G. K. Owens, Regulation of differentiation of vascular smooth muscle cells Physiological Reviews. ,vol. 75, pp. 487- 517 ,(1995) , 10.1152/PHYSREV.1995.75.3.487
Terence D Allen, Ana M Schor, Andrew B Sutton, E Arciniegas, Transforming growth factor beta 1 promotes the differentiation of endothelial cells into smooth muscle-like cells in vitro Journal of Cell Science. ,vol. 103, pp. 521- 529 ,(1992)
Masanori Aikawa, Palanisamy Nalla Sivam, Makoto Kuro-o, Kenjiro Kimura, KI Nakahara, SI Takewaki, Makiko Ueda, Hiroshi Yamaguchi, Yoshio Yazaki, Muthu Periasamy, None, Human smooth muscle myosin heavy chain isoforms as molecular markers for vascular development and atherosclerosis. Circulation Research. ,vol. 73, pp. 1000- 1012 ,(1993) , 10.1161/01.RES.73.6.1000
Michael A. Gimbrone, Ramzi S. Cotran, Judah Folkman, HUMAN VASCULAR ENDOTHELIAL CELLS IN CULTURE Growth and DNA Synthesis Journal of Cell Biology. ,vol. 60, pp. 673- 684 ,(1974) , 10.1083/JCB.60.3.673