Research progress in cytokines and signaling pathways for promoting pulmonary angiogenesis and vascular development
MA Xing-Na, LI Qiu-Ping, FENG Zhi-Chun
Department of Neonatal Intensive Care Unit, Bayi Children’s Hospital Affiliated to General Hospital of Beijing Military Command of People's Liberation Army, Beijing 100007, China
Abstract：With the advances in pre- and post-natal medical care, the incidence of bronchopulmonary dysplasia (BPD) is on the rise, while its pathogenesis remains not clear. New BPD theory shows that the core pathogenesis of BPD is simple alveolar structure and pulmonary microvascular abnormalities that eventually lead to reduced pulmonary gas exchange, so the research on pulmonary microvascular development was gradually taken seriously. Pulmonary angiogenesis and vascular development require the participation of various cytokines and signaling pathways, the most important of which include VEGF/VEGFR pathway, Ang/Tie pathway, Ephrins/Eph pathway, and Notch/Jagged1 pathway. These cytokines and signaling pathways play important roles in pulmonary vascular development.
MA Xing-Na,LI Qiu-Ping,FENG Zhi-Chun. Research progress in cytokines and signaling pathways for promoting pulmonary angiogenesis and vascular development[J]. CJCP, 2013, 15(9): 800-805.
Steven H, Abman MD. Bronchopulmonary dysplasia "a vascular hypothesis"[J]. Am J Respir Crit Care Med, 2001, 164(10): 1755-1756.
[2]
Morrisey EE, Hogan BL. Preparing for the first breath: genetic and cellular mechanisms in lung development[J]. Dev Cell, 2010, 18(1): 8-23.
[3]
Gaengel K, Genove G, Armulik A, Betsholtz C. Endothelial-mural cell signaling in vascular development and angiogenesis[J]. Arterioscler Thromb Vasc Biol, 2009, 29(5): 630-638.
Abman SH. Impaired vascular endothelial growth factor signaling in the pathogenesis of neonatal pulmonary vascular disease[J]. Adv Exp Med and Biol, 2010, 661: 323-335.
[6]
Koch S, Claesson-Welsh L. Signal transduction by vascular endothelial growth factor receptors[J]. Cold Spring Harb Perspect Med, 2012, 2(7): a006502.
[7]
Ikeda H, Shiojima I, Oka T, Yoshida M, Maemura K, Walsh K, et al. Increased Akt-mTOR signaling in lung epithelium is associated with respiratory distress syndrome in mice[J]. Mol Cell Biol, 2011, 31(5): 1054-1065.
[8]
Stahmann N, Woods A, Spengler K, Heslegrave A, Bauer R, Krause S, et al. Activation of AMP-activated protein kinase by vascular endothelial growth factor mediates endothelial angiogenesis independently of nitric-oxide synthase[J]. J Biol Chem, 2010, 285(14): 10638-10652.
[9]
Li X, Claesson-Welsh L, Shibuya M. VEGF receptor signal transduction[J]. Methods Enzymol, 2008, 443: 261-284.
[10]
Sato TN, Tozawa Y, Deutsch U, Wolburgbuchholz K,Fujiwara Y,Gendronmaguire M, et al. Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation[J]. Am J Respir Cell Mol Biol, 1995, 376(6535): 70-74.
Hato T, Kimura Y, Morisada T, Kohd GY, Miyatae K, Tabatae M, et al. Angiopoietins contribute to lung development by regulating pulmonary vascular network formation[J]. Biochem Biophys Res Commun, 2009, 381(2): 218-223.
[13]
van der Heijden M, van Nieuw Amerongen GP, Chedamni S, van Hinsbergh VW, Johan Groeneveld AB. The angiopoietin-Tie2 system as a therapeutic target in sepsis and acute lung injury[J]. Expert Opin Ther Targets, 2009, 13(1): 39-53.
[14]
Ong T, McClintock DE, Kallet RH, Ware LB, Matthay MA, Liu KD. Ratio of angiopoietin-2 to angiopoietin-1 as a predictor of mortality in acute lung injury patients[J]. Crit Care Med, 2010, 38(9): 1845-1851.
[15]
Yuan HT, Khankin EV, Karumanchi SA, Parikh SM. Angiopoietin 2 is a partial agonist/antagonist of Tie2 signaling in the endothelium[J]. Mol Cell Biol, 2009, 29(12): 3451.
[16]
Hu B, Cheng SY. Angiopoietin-2: development of inhibitors for cancer therapy[J]. Curr Oncol Rep, 2009, 11(2): 111-116.
[17]
Thomas M, Augustin HG. The role of the Angiopoietins in vascular morphogenesis[J]. Angiogenesis, 2009, 12(2): 125-37.
[18]
Karar J, Maity A. PI3K/AKT/mTOR pathway in angiogenesis[J]. Front Mol Neurosci, 2011, 4(51): 1-8.
[19]
Trouillon R, Kang DK, Park H, Chang SI, O'Hare D. Angiogenin induces nitric oxide synthesis in endothelial cells through PI-3 and Akt kinases[J]. Biochemistry, 2010, 49(15): 3282-3288.
[20]
Trouillon R, Kang DK, Chang SI, O'Hare D. Angiogenin induces nitric oxide release independently from its RNase activity[J]. Chem Commun, 2011, 47: 3421-3423.
[21]
Bhandari V, Choo-Wing R, Harijith A, Sun H, Syed MA, Homer RJ, et al. Increased hyperoxia-induced lung injury in nitric oxide synthase 2 null mice is mediated via angiopoietin 2[J]. Am J Respir Cell Mol Biol, 2012, 46(5): 668-676.
[22]
Azab F, Azab AK, Maiso P, Calimeri T, Flores L, Liu Y, et al. Eph-B2/Ephrin-B2 interaction plays a major role in the adhesion and proliferation of waldenstrom's macroglobulinemia[J]. Clin Cancer Res, 2012, 18(1): 91-104.
[23]
Kandouz M. The Eph/Ephrin family in cancer metastasis: communication at the service of invasion[J]. Cancer Metastasis Rev, 2012, 31(1-2): 353-373.
[24]
Mosch B, Reissenweber B, Neuber C, Pietzsch J. Eph receptors and ephrin ligands: important players in angiogenesis and tumor angiogenesis[J]. J Oncol, 2010: 135285.
[25]
Salvucci O, Tosato G. Essential roles of EphB receptors and EphrinB ligands in endothelial cell function and angiogenesis[J]. Adv Cancer Res, 2012, 114: 21-57.
[26]
Wilkinson GA, Schittny JC, Reinhardt DP, Klein R. Role for ephrinB2 in postnatal lung alveolar development and elastic matrix integrity[J]. Dev Dyn, 2008, 237(8): 2220-2234.
[27]
Vadivel A, van Haaften T, Alphonse RS, Rey-Parra GJ, Ionescu L, Haromy A. Critical role of the axonal guidance cue EphrinB2 in lung growth, angiogenesis, and repair[J]. Am J Respir Crit Care Med, 2012, 185(5): 564-574.
[28]
Carpenter TC, Schroeder W, Stenmark KR, Schmidt EP. Eph-A2 promotes permeability and inflammatory responses to bleomycin-induced lung injury[J]. Am J Respir Cell Mol Biol, 2012, 46(1): 40-47.
Yu LN, Zhou XL, Yu J, Huang H, Jiang LS, Zhang FJ, et al. PI3K contributed to modulation of spinal nociceptive information related to ephrinBs/EphBs[J]. PLoS One, 2012, 7(8): e40930.
[31]
Hruska M, Dalva MB. Ephrin regulation of synapse formation, function and plasticity[J]. Mol Cell Neurosci, 2012, 50(1): 35-44.
[32]
Xiao Z, Carrasco R, Kinneer K, Sabol D, Jallal B, Coats S, et al. EphB4 promotes or suppresses Ras/MEK/ERK pathway in a context-dependent manner: implications for EphB4 as a cancer target[J]. Cancer Biol Ther, 2012, 13(8): 630-637.
[33]
Pasquale EB. Eph receptors and ephrins in cancer: bidirectional signaling and beyond[J]. Nat Rev Cancer, 2010, 10(3): 165-180.
[34]
Roca C, Adams RH. Regulation of vascular morphogenesis by Notch signaling[J]. Genes, 2007, 21: 2511-2524.
Chang ACY. Investigation of Notch and nitric oxide signaling in the cardiovascular system[D]. Experimental Medicine, University of British Columbia, 2012.
[37]
Fortini ME. Notch signaling: the core pathway and its posttranslational regulation[J]. Dev Cell, 2009, 16(5): 633-647.
[38]
Kopan R, Ilagan MXG. The canonical Notch signaling pathway: unfolding the activation mechanism[J]. Cell, 2009, 137(2): 216-233.
[39]
Kunig AM, Balasubramaniam V, Markham NE, Morgan D, Montgomery G, Grover TR, et al. Recombinant human VEGF treatment enhances alveolarization after hyperoxic lung injury in neonatal rats[J]. Am J Physiol Lung Cell Mol Physiol, 2005, 289(4): L529-L535.
[40]
Kunig AM, Balasubramaniam V, Markham NE, Seedorf G, Gien J, Abman SH. Recombinant human VEGF treatment transiently increases lung edema but enhances lung structure after neonatal hyperoxia[J]. Am J Physiol Lung Cell Mol Physiol, 2006, 291(5): L1068-L1078.
[41]
Tropea K, Christou H. Current pharmacologic approaches for prevention and treatment of bronchopulmonary dysplasia[J]. Int J Pediatr, 2012: 598606.
[42]
Mercier JC, Olivier P, Loron G, Fontaine R, Maury L, Baud O. Inhaled nitric oxide to prevent bronchopulmonary dysplasia in preterm neonates[J]. Semin Fetal Neonatal Med, 2009, 14(1): 28-34.
[43]
Soll RF. Inhaled Nitric Oxide for respiratory failure in preterm infants[J]. Neonatology, 2012, 102(4): 251-253
