LKB1 in endothelial cells is required for angiogenesis and TGFβ-mediated vascular smooth muscle cell recruitment

作者: A. Londesborough , K. Vaahtomeri , M. Tiainen , P. Katajisto , N. Ekman

DOI: 10.1242/DEV.017038

关键词:

摘要: Inactivation of the tumor suppressor kinase Lkb1 in mice leads to vascular defects and midgestational lethality at embryonic day 9-11 (E9-E11). Here, we have used conditional targeting investigate underlying Lkb1(-/-) phenotype. Endothelium-restricted deletion led death E12.5 with a loss smooth muscle cells (vSMCs) disruption. Transforming growth factor beta (TGFbeta) pathway activity was reduced Lkb1-deficient endothelial (ECs), TGFbeta signaling from ECs adjacent mesenchyme defective, noted as SMAD2 phosphorylation. The addition mutant yolk sac explants rescued vSMCs, evidenced by alpha actin (SMA) expression. These results reveal an essential function for TGFbeta-mediated vSMC recruitment during angiogenesis.

参考文章(44)
P A Campochiaro, S F Hackett, Modulation of plasminogen activator inhibitor-1 and urokinase in retinal pigmented epithelial cells Investigative Ophthalmology & Visual Science. ,vol. 34, pp. 2055- 2061 ,(1993)
E Van Obberghen-Schilling, N S Roche, K C Flanders, M B Sporn, A B Roberts, Transforming growth factor beta 1 positively regulates its own expression in normal and transformed cells. Journal of Biological Chemistry. ,vol. 263, pp. 7741- 7746 ,(1988) , 10.1016/S0021-9258(18)68561-8
Lisa D. Urness, Lise K. Sorensen, Dean Y. Li, Arteriovenous malformations in mice lacking activin receptor-like kinase-1 Nature Genetics. ,vol. 26, pp. 328- 331 ,(2000) , 10.1038/81634
Akseli Hemminki, David Markie, Ian Tomlinson, Egle Avizienyte, Stina Roth, Anu Loukola, Graham Bignell, William Warren, Maria Aminoff, Pia Höglund, Heikki Järvinen, Paula Kristo, Katarina Pelin, Maaret Ridanpää, Reijo Salovaara, Tumi Toro, Walter Bodmer, Sylviane Olschwang, Anne S Olsen, Michael R Stratton, Albert De La Chapelle, Lauri A Aaltonen, None, A serine/threonine kinase gene defective in Peutz–Jeghers syndrome Nature. ,vol. 391, pp. 184- 187 ,(1998) , 10.1038/34432
C. Brakebusch, E. Gustafsson, K. Hietanen, R. Fassler, Tie-1-directed expression of Cre recombinase in endothelial cells of embryoid bodies and transgenic mice. Journal of Cell Science. ,vol. 114, pp. 671- 676 ,(2001) , 10.1242/JCS.114.4.671
Per Lindahl, Bengt R Johansson, Per Leveen, Christer Betsholtz, Pericyte loss and microaneurysm formation in PDGF-B-deficient mice Science. ,vol. 277, pp. 242- 245 ,(1997) , 10.1126/SCIENCE.277.5323.242
Pekka Katajisto, Tea Vallenius, Kari Vaahtomeri, Niklas Ekman, Lina Udd, Marianne Tiainen, Tomi P. Mäkelä, The LKB1 tumor suppressor kinase in human disease. Biochimica et Biophysica Acta. ,vol. 1775, pp. 63- 75 ,(2007) , 10.1016/J.BBCAN.2006.08.003
D. Y. Li, Defective Angiogenesis in Mice Lacking Endoglin Science. ,vol. 284, pp. 1534- 1537 ,(1999) , 10.1126/SCIENCE.284.5419.1534
Nabeel Bardeesy, Manisha Sinha, Aram F. Hezel, Sabina Signoretti, Nathaniel A. Hathaway, Norman E. Sharpless, Massimo Loda, Daniel R. Carrasco, Ronald A. DePinho, Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but resistance to transformation Nature. ,vol. 419, pp. 162- 167 ,(2002) , 10.1038/NATURE01045