Pleiotropic role of VEGF-A in regulating fetal pulmonary mesenchymal cell turnover

作者: S. Majka , K. Fox , B. McGuire , J. Crossno , P. McGuire

DOI: 10.1152/AJPLUNG.00175.2005

关键词: Lung morphogenesisAutocrine signallingCell biologyParacrine signallingReceptorCellBiologyCell cycleContact inhibitionMesenchymal stem cell

摘要: Tight regulation of VEGF-A production and signaling is important for the maintenance lung development homeostasis. VEGF null mice have provided little insight into role during later stages morphogenesis. Therefore, we examined in vitro effects autocrine paracrine inhibition on a Flk-1-negative subset fetal pulmonary mesenchymal cells (pMC). We hypothesized that receptor regulates turnover mesenchyme cell cycle-dependent manner. blockade with SU-5416 caused spreading decreased proliferation bcl-2 localization. Nuclear expression cycle inhibitory protein, p21, was increased treatment, p27 absent. Autocrine by pMC resulted p21/p27-dependent contact inhibition. In contrast, exogenous progression through cycle. Selective activation Flt placental growth factor demonstrated importance this receptor/kinase responsiveness pMC. The localization survival dependent VEGF. These results provide evidence plays critical proliferation, survival, subsequent normal architecture control.

参考文章(54)
C Langston, M Reed, W M Thurlbeck, K Kida, Human lung growth in late gestation and in the neonate. The American review of respiratory disease. ,vol. 129, pp. 607- 613 ,(1984)
Steven H. Abman, Jessie R. Groothius, Pathophysiology and treatment of bronchopulmonary dysplasia. Current issues. Pediatric Clinics of North America. ,vol. 41, pp. 277- 315 ,(1994) , 10.1016/S0031-3955(16)38726-0
Carl T D'Angio, The role of vascular growth factors in hyperoxia-induced injury to the developing lung Frontiers in Bioscience. ,vol. 7, pp. d1609- 1623 ,(2002) , 10.2741/A865
ABHAY J. BHATT, GLORIA S. PRYHUBER, HEIDIE HUYCK, RICHARD H. WATKINS, LEON A. METLAY, WILLIAM M. MANISCALCO, Disrupted pulmonary vasculature and decreased vascular endothelial growth factor, Flt-1, and TIE-2 in human infants dying with bronchopulmonary dysplasia. American Journal of Respiratory and Critical Care Medicine. ,vol. 164, pp. 1971- 1980 ,(2001) , 10.1164/AJRCCM.164.10.2101140
Lori E. Kotch, Narayan V. Iyer, Erik Laughner, Gregg L. Semenza, Defective Vascularization of HIF-1α-Null Embryos Is Not Associated with VEGF Deficiency but with Mesenchymal Cell Death Developmental Biology. ,vol. 209, pp. 254- 267 ,(1999) , 10.1006/DBIO.1999.9253
Markus Grompe, Anthony N. Karnezis, Marina Dorokhov, Liang Zhu, Loss of p27Kip1 enhances the transplantation efficiency of hepatocytes transferred into diseased livers Journal of Clinical Investigation. ,vol. 108, pp. 383- 390 ,(2001) , 10.1172/JCI11933
Sarah A. Gebb, John M. Shannon, Tissue interactions mediate early events in pulmonary vasculogenesis. Developmental Dynamics. ,vol. 217, pp. 159- 169 ,(2000) , 10.1002/(SICI)1097-0177(200002)217:2<159::AID-DVDY3>3.0.CO;2-9
Akihiko Hara, Cheryl J Chapin, Robert Ertsey, Joseph A Kitterman, Changes in fetal lung distension alter expression of vascular endothelial growth factor and its isoforms in developing rat lung. Pediatric Research. ,vol. 58, pp. 30- 37 ,(2005) , 10.1203/01.PDR.0000163614.20031.C5
James M. Greenberg, Felisa Y. Thompson, Sherry K. Brooks, John M. Shannon, Kathleen McCormick-Shannon, James E. Cameron, Bradford P. Mallory, Ann L. Akeson, Mesenchymal expression of vascular endothelial growth factors D and A defines vascular patterning in developing lung. Developmental Dynamics. ,vol. 224, pp. 144- 153 ,(2002) , 10.1002/DVDY.10095