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PPARγ activation in late gestation does not promote surfactant maturation in the fetal sheep lung

Published online by Cambridge University Press:  07 January 2021

Jiaqi Ren Open the ORCID record for Jiaqi Ren [Opens in a new window] ,
Mitchell C. Lock ,
Jack R. T. Darby Open the ORCID record for Jack R. T. Darby [Opens in a new window] ,
Sandra Orgeig Open the ORCID record for Sandra Orgeig [Opens in a new window] ,
Stacey L. Holman ,
Megan Quinn ,
Mike Seed ,
Beverly S. Muhlhausler ,
I. Caroline McMillen  and
Janna L. Morrison Open the ORCID record for Janna L. Morrison [Opens in a new window]
Jiaqi Ren
Affiliation:
Department of Physiology, University of Toronto, Toronto, ON, Canada Early Origins of Adult Health Research Group, Health and Biomedical Innovation, UniSA: Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia Hospital for Sick Children, Toronto, ON, Canada
Mitchell C. Lock
Affiliation:
Early Origins of Adult Health Research Group, Health and Biomedical Innovation, UniSA: Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia
Jack R. T. Darby
Affiliation:
Early Origins of Adult Health Research Group, Health and Biomedical Innovation, UniSA: Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia
Sandra Orgeig
Affiliation:
Cancer Research Institute, UniSA: Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia
Stacey L. Holman
Affiliation:
Early Origins of Adult Health Research Group, Health and Biomedical Innovation, UniSA: Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia
Megan Quinn
Affiliation:
Early Origins of Adult Health Research Group, Health and Biomedical Innovation, UniSA: Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia
Mike Seed
Affiliation:
Department of Physiology, University of Toronto, Toronto, ON, Canada Hospital for Sick Children, Toronto, ON, Canada
Beverly S. Muhlhausler
Affiliation:
CSIRO, University of Adelaide, Adelaide, SA, Australia
I. Caroline McMillen
Affiliation:
Early Origins of Adult Health Research Group, Health and Biomedical Innovation, UniSA: Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia
Janna L. Morrison*
Affiliation:
Early Origins of Adult Health Research Group, Health and Biomedical Innovation, UniSA: Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia
*
Address for correspondence: Janna L. Morrison, Australian Research Council Future Fellow, Early Origins of Adult Health Research Group, Health and Biomedical Innovation, UniSA: Clinical and Health Sciences, University of South Australia, GPO Box 2471, Adelaide, SA, Australia5001. Email: [email protected]
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Abstract

Respiratory distress syndrome results from inadequate functional pulmonary surfactant and is a significant cause of mortality in preterm infants. Surfactant is essential for regulating alveolar interfacial surface tension, and its synthesis by Type II alveolar epithelial cells is stimulated by leptin produced by pulmonary lipofibroblasts upon activation by peroxisome proliferator-activated receptor γ (PPARγ). As it is unknown whether PPARγ stimulation or direct leptin administration can stimulate surfactant synthesis before birth, we examined the effect of continuous fetal administration of either the PPARγ agonist, rosiglitazone (RGZ; Study 1) or leptin (Study 2) on surfactant protein maturation in the late gestation fetal sheep lung. We measured mRNA expression of genes involved in surfactant maturation and showed that RGZ treatment reduced mRNA expression of LPCAT1 (surfactant phospholipid synthesis) and LAMP3 (marker for lamellar bodies), but did not alter mRNA expression of PPARγ, surfactant proteins (SFTP-A, -B, -C, and -D), PCYT1A (surfactant phospholipid synthesis), ABCA3 (phospholipid transportation), or the PPARγ target genes SPHK-1 and PAI-1. Leptin infusion significantly increased the expression of PPARγ and IGF2 and decreased the expression of SFTP-B. However, mRNA expression of the majority of genes involved in surfactant synthesis was not affected. These results suggest a potential decreased capacity for surfactant phospholipid and protein production in the fetal lung after RGZ and leptin administration, respectively. Therefore, targeting PPARγ may not be a feasible mechanistic approach to promote lung maturation.

Keywords

rosiglitazoneleptinPPARγsurfactant maturationrespiratory distress syndrome
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 12 , Issue 6 , December 2021 , pp. 963 - 974
Copyright
© The Author(s), 2021. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

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References

Fanaroff, AA, Wright, LL, Stevenson, DK, et al. Very-low-birth-weight outcomes of the National Institute of Child Health and Human Development Neonatal Research Network, May 1991 through December 1992. Am J Obstet Gynecol. 1995; 173(5), 1423–1431.CrossRefGoogle Scholar
Nkadi, PO, Merritt, TA, Pillers, D-AM. An overview of pulmonary surfactant in the neonate: genetics, metabolism, and the role of surfactant in health and disease. Mol Genet Metab. 2009; 97(2), 95–101.CrossRefGoogle ScholarPubMed
Burri, PH. Fetal and postnatal development of the lung. Annu Rev Physiol. 1984; 46, 617–628.CrossRefGoogle ScholarPubMed
Poulain, FR, Clements, JA. Pulmonary surfactant therapy. West J Med. 1995; 162(1), 43–50.Google ScholarPubMed
Veldhuizen, R, Nag, K, Orgeig, S, Possmayer, F. The role of lipids in pulmonary surfactant. Biochim Biophys Acta. 1998; 1408(2–3), 90–108.CrossRefGoogle ScholarPubMed
Orgeig, S, Morrison, JL, Daniels, CB. Evolution, development, and function of the pulmonary surfactant system in normal and perturbed environments. Compr Physiol. 2015; 6(1), 363–422.CrossRefGoogle ScholarPubMed
Liggins, GC, Howie, RN. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics. 1972; 50(4), 515–525.CrossRefGoogle ScholarPubMed
Bonanno, C, Wapner, RJ. Antenatal corticosteroids in the management of preterm birth: are we back where we started? Obstet Gynecol Clin North Am. 2012; 39(1), 47–63.CrossRefGoogle ScholarPubMed
McGillick, EV, Orgeig, S, Williams, MT, Morrison, JL. Risk of respiratory distress syndrome and efficacy of glucocorticoids: are they the same in the normally grown and growth-restricted infant? Reprod Sci. 2016; 23(11), 1459–1472.CrossRefGoogle ScholarPubMed
Polin, RA, Carlo, WA, Committee on Fetus and Newborn. Surfactant replacement therapy for preterm and term neonates with respiratory distress. Am Acad Pediatr. 2014; 133(1), 156–163.Google ScholarPubMed
Stuart, S, McMillan, D. Surfactant use outside the tertiary care centre. Paediatr Child Health. 2005; 10(2), 100–102.Google ScholarPubMed
Raju, TNK, Langenberg, P. Pulmonary hemorrhage and exogenous surfactant therapy: a metaanalysis. J Pediatr. 1993; 123(4), 603–610.CrossRefGoogle ScholarPubMed
Ferré, P. The biology of peroxisome proliferator-activated receptors: relationship with lipid metabolism and insulin sensitivity. Diabetes. 2004; 53(SUPPL. 1), S43–S50.CrossRefGoogle ScholarPubMed
Lehmann, JM, Moore, LB, Smith-Oliver, TA, Wilkison, WO, Willson, TM, Kliewer, SA. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor γ (PPARγ). J Biol Chem. 1995; 270(22), 12953–12959.CrossRefGoogle Scholar
Tontonoz, P, Spiegelman, BM. Fat and beyond: the diverse biology of PPARγ. Annu Rev Biochem. 2008; 77, 289–312.CrossRefGoogle ScholarPubMed
Tyagi, S, Gupta, P, Saini, AS, Kaushal, C, Sharma, S. The peroxisome proliferator-activated receptor: a family of nuclear receptors role in various diseases. J Adv Pharm Technol Res. 2011; 2(4), 236–240.CrossRefGoogle ScholarPubMed
Rehan, VK, Torday, JS. PPARγ signaling mediates the evolution, development, homeostasis, and repair of the lung. PPAR Res. 2012; 2012, 289867.CrossRefGoogle ScholarPubMed
Oruqaj, L, Forst, S, Schreckenberg, R, et al. Effect of high fat diet on pulmonary expression of parathyroid hormone-related protein and its downstream targets. Heliyon. 2016; 2(10), e00182.CrossRefGoogle ScholarPubMed
Rehan, VK, Wang, Y, Patel, S, Santos, J, Torday, JS. Rosiglitazone, a peroxisome proliferator-activated receptor-γ agonist, prevents hyperoxia-induced neonatal rat lung injury in vivo. Pediatr Pulmonol. 2006; 41(6), 558–569.CrossRefGoogle ScholarPubMed
Torday, JS, Rehan, VK. Stretch-Stimulated surfactant synthesis is coordinated by the paracrine actions of PTHrP and leptin. Am J Physiol Lung Cell Mol Physiol. 2002; 283(1), L130–L135.CrossRefGoogle ScholarPubMed
Torday, JS, Torday, DP, Gutnick, J, Qin, J, Rehan, V. Biologic role of fetal lung fibroblast triglycerides as antioxidants. Pediatr Res. 2001; 49(6), 843–849.CrossRefGoogle ScholarPubMed
Torday, JS, Torres, E, Rehan, VK. The role of fibroblast transdifferentiation in lung epithelial cell proliferation, differentiation, and repair in vitro. Pediatr Pathol Mol Med. 2003; 22(3), 189–207.CrossRefGoogle ScholarPubMed
Lecarpentier, Y, Gourrier, E, Gobert, V, Vallée, A. Bronchopulmonary dysplasia: crosstalk between PPARγ, Wnt/β-catenin and TGF-β pathways; the potential therapeutic role of PPARγ agonists. Front Pediatr. 2019; 7, 176.CrossRefGoogle ScholarPubMed
Lee, HJ, Lee, YJ, Choi, CW, et al. Rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, restores alveolar and pulmonary vascular development in a rat model of bronchopulmonary dysplasia. Yonsei Med J. 2014; 55(1), 99–106.CrossRefGoogle Scholar
Morales, E, Sakurai, R, Husain, S, et al. Nebulized PPARγ agonists: a novel approach to augment neonatal lung maturation and injury repair in rats. Pediatr Res. 2014; 75(5), 631–640.CrossRefGoogle ScholarPubMed
Muhlhausler, BS, Morrison, JL, McMillen, IC. Rosiglitazone increases the expression of peroxisome proliferator-activated receptor-gamma target genes in adipose tissue, liver, and skeletal muscle in the sheep fetus in late gestation. Endocrinology. 2009; 150(9), 4287–4294.CrossRefGoogle ScholarPubMed
Torday, JS, Sun, H, Wang, L, Torres, E. Leptin mediates the parathyroid hormone-related protein paracrine stimulation of fetal lung maturation. Am J Physiol - Lung Cell Mol Physiol. 2002; 282(3), L405–L410.CrossRefGoogle ScholarPubMed
Kirwin, SM, Bhandari, V, Dimatteo, D, et al. Leptin enhances lung maturity in the fetal rat. Pediatr Res. 2006; 60(2), 200–204.CrossRefGoogle ScholarPubMed
Chen, H, Zhang, J-P, Huang, H, Wang, Z-H, Cheng, R, Cai, W-B. Leptin promotes fetal lung maturity and upregulates SP-A expression in pulmonary alveoli type-II epithelial cells involving TTF-1 activation. PLoS One. 2013; 8(7), e69297.CrossRefGoogle ScholarPubMed
De Blasio, MJ, Boije, M, Kempster, SL, et al. Leptin matures aspects of lung structure and function in the ovine fetus. Endocrinology. 2016; 157(1), 395–404.CrossRefGoogle ScholarPubMed
Grundy, D. Principles and standards for reporting animal experiments in The Journal of Physiology and Experimental Physiology. Exp Physiol. 2015; 100(7), 755–758.CrossRefGoogle ScholarPubMed
Russell, WMS, Burch, RL. The Principles of Humane Experimental Technique, 1959.Google Scholar
Mühlhäusler, BS, Roberts, CT, McFarlane, JR, Kauter, KG, McMillen, IC. Fetal leptin is a signal of fat mass independent of maternal nutrition in ewes fed at or above maintenance energy requirements. Biol Reprod. 2002; 67(2), 493–499.CrossRefGoogle ScholarPubMed
Edwards, LJ, McMillen, IC. Maternal undernutrition increases arterial blood pressure in the sheep fetus during late gestation. J Physiol. 2001; 533(2), 561–570.CrossRefGoogle ScholarPubMed
Bazargan, M, Foster, DJR, Muhlhausler, BS, Morrison, JL, McMillen, IC, Davey, AK. Limited fetal metabolism of rosiglitazone: elimination via the maternal compartment in the pregnant ewe. Reprod Toxicol. 2016; 61, 162–168.CrossRefGoogle ScholarPubMed
Yuen, BS, Owens, PC, Muhlhausler, BS, et al. Leptin alters the structural and functional characteristics of adipose tissue before birth. FASEB J. 2003; 17(9), 1102–1104.CrossRefGoogle ScholarPubMed
Bustin, SA, Benes, V, Garson, JA, et al. The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem. 2009; 55(4), 611–622.CrossRefGoogle ScholarPubMed
McGillick, EV, Orgeig, S, Morrison, JL. Structural and molecular regulation of lung maturation by intratracheal vascular endothelial growth factor administration in the normally grown and placentally restricted fetus. J Physiol. 2016; 594(5), 1399–1420.CrossRefGoogle ScholarPubMed
Lock, MC, McGillick, EV, Orgeig, S, et al. Differential effects of late gestation maternal overnutrition on the regulation of surfactant maturation in fetal and postnatal life. J Physiol. 2017; 595(21), 6635–6652.CrossRefGoogle ScholarPubMed
McGillick, EV, Orgeig, S, Caroline McMillen, I, Morrison, JL. The fetal sheep lung does not respond to cortisol infusion during the late canalicular phase of development. Physiol Rep. 2013; 1(6), e00130.CrossRefGoogle Scholar
Vandesompele, J, De Preter, K, Pattyn, F, et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002; 3(7), research0034.1–0034.11.CrossRefGoogle ScholarPubMed
Soo, PS, Hiscock, J, Botting, KJ, Roberts, CT, Davey, AK, Morrison, JL. Maternal undernutrition reduces P-glycoprotein in guinea pig placenta and developing brain in late gestation. Reprod Toxicol. 2012; 33(3), 374–381.CrossRefGoogle ScholarPubMed
Passmore, M, Nataatmadja, M, Fraser, JF. Selection of reference genes for normalisation of real-time RT-PCR in brain-stem death injury in Ovis aries. BMC Mol Biol. 2009; 10, 72.CrossRefGoogle ScholarPubMed
Orgeig, S, Crittenden, TA, Marchant, C, McMillen, IC, Morrison, JL. Intrauterine growth restriction delays surfactant protein maturation in the sheep fetus. Am J Physiol Lung Cell Mol Physiol. 2010; 298(4), L575–L583.CrossRefGoogle ScholarPubMed
Orgeig, S, McGillick, EV, Botting, KJ, Zhang, S, McMillen, IC, Morrison, JL. Increased lung prolyl hydroxylase and decreased glucocorticoid receptor are related to decreased surfactant protein in the growth-restricted sheep fetus. Am J Physiol Cell Mol Physiol. 2015; 309(1), L84–L97.CrossRefGoogle ScholarPubMed
Muhlhausler, BS, Duffield, JA, McMillen, IC. Increased maternal nutrition stimulates peroxisome proliferator activated receptor-gamma, adiponectin, and leptin messenger ribonucleic acid expression in adipose tissue before birth. Endocrinology. 2007; 148(2), 878–885.CrossRefGoogle ScholarPubMed
Soo, JY, Orgeig, S, McGillick, EV, Zhang, S, McMillen, IC, Morrison, JL. Normalisation of surfactant protein -A and -B expression in the lungs of low birth weight lambs by 21 days old. PLoS One. 2017; 12(9), e0181185.CrossRefGoogle Scholar
Wang, KCW, Lim, CH, McMillen, IC, Duffield, JA, Brooks, DA, Morrison, JL. Alteration of cardiac glucose metabolism in association to low birth weight: experimental evidence in lambs with left ventricular hypertrophy. Metabolism. 2013; 62(11), 1662–1672.CrossRefGoogle ScholarPubMed
Zhang, S, Barker, P, Botting, KJ, et al. Early restriction of placental growth results in placental structural and gene expression changes in late gestation independent of fetal hypoxemia. Physiol Rep. 2016; 4(23), e13049.CrossRefGoogle ScholarPubMed
Gentili, S, Morrison, JL, McMillen, IC. Intrauterine growth restriction and differential patterns of hepatic growth and expression of IGF1, PCK2, and HSDL1 mRNA in the sheep fetus in late gestation. Biol Reprod. 2009; 80(6), 1121–1127.CrossRefGoogle ScholarPubMed
Botting, KJ, Caroline McMillen, I, Forbes, H, Nyengaard, JR, Morrison, JL. Chronic hypoxemia in late gestation decreases cardiomyocyte number but does not change expression of hypoxia-responsive genes. J Am Heart Assoc. 2014; 3(4), e000531.CrossRefGoogle Scholar
Wang, KCW, Brooks, DA, Summers-Pearce, B, et al. Low birth weight activates the renin–angiotensin system, but limits cardiac angiogenesis in early postnatal life. Physiol Rep. 2015; 3(2), e12270.CrossRefGoogle ScholarPubMed
Morrison, JL, Botting, KJ, Soo, PS, et al. Antenatal steroids and the IUGR fetus: are exposure and physiological effects on the lung and cardiovascular system the same as in normally grown fetuses? J Pregnancy. 2012; 2012, 839656.CrossRefGoogle ScholarPubMed
Lock, MC, McGillick, EV, Orgeig, S, Zhang, S, McMillen, IC, Morrison, JL. Mature surfactant protein-B expression by immunohistochemistry as a marker for surfactant system development in the fetal sheep lung. J Histochem Cytochem. 2015; 63(11), 866–878.CrossRefGoogle ScholarPubMed
McGillick, EV, Orgeig, S, Morrison, JL. Regulation of lung maturation by prolyl hydroxylase domain inhibition in the lung of the normally grown and placentally restricted fetus in late gestation. Am J Physiol Regul Integr Comp Physiol. 2016; 310, R1226–R1243.CrossRefGoogle ScholarPubMed
Brüel, A, Oxlund, H, Nyengaard, JR. The total length of myocytes and capillaries, and total number of myocyte nuclei in the rat heart are time-dependently increased by growth hormone. Growth Horm IGF Res. 2005; 15(4), 256–264.CrossRefGoogle ScholarPubMed
McGillick, EV, Morrison, JL, McMillen, IC, Orgeig, S. Intrafetal glucose infusion alters glucocorticoid signaling and reduces surfactant protein mRNA expression in the lung of the late-gestation sheep fetus. Am J Physiol Regul Integr Comp Physiol. 2014; 307(5), R538–R545.CrossRefGoogle ScholarPubMed
Braissant, O, Foufelle, F, Scotto, C, Dauça, M, Wahli, W. Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-α, -β, and -γ in the adult rat. Endocrinology. 1996; 137(1), 354–366.CrossRefGoogle ScholarPubMed
Lee, H, Shi, W, Tontonoz, P, et al. Role for peroxisome proliferator-activated receptor alpha in oxidized phospholipid-induced synthesis of monocyte chemotactic protein-1 and interleukin-8 by endothelial cells. Circ Res. 2000; 87(6), 516–521.CrossRefGoogle ScholarPubMed
Pawlak, M, Lefebvre, P, Staels, B. Molecular mechanism of PPARα action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease. J Hepatol. 2015; 62(3), 720–733.CrossRefGoogle ScholarPubMed
Van Raalte, DH, Li, M, Pritchard, PH, Wasan, KM. Peroxisome proliferator-activated receptor (PPAR)-α: a pharmacological target with a promising future. Pharm Res. 2004; 21(9), 1531–1538.CrossRefGoogle ScholarPubMed
Liang, H, Ward, WF. PGC-1α: a key regulator of energy metabolism. Adv Physiol Educ. 2006; 30(4), 141–151.CrossRefGoogle ScholarPubMed
Wang, Y, Santos, J, Sakurai, R, et al. Peroxisome proliferator-activated receptor gamma agonists enhance lung maturation in a neonatal rat model. Pediatr Res. 2009; 65(2), 150–155.CrossRefGoogle Scholar
Joshi, S, Kotecha, S. Lung growth and development. Early Hum Dev. 2007; 83(12), 789–794.CrossRefGoogle ScholarPubMed
Lock, M, McGillick, EV, Orgeig, S, McMillen, IC, Morrison, JL. Regulation of fetal lung development in response to maternal overnutrition. Clin Exp Pharmacol Physiol. 2013; 40(11), 803–816.CrossRefGoogle ScholarPubMed
Schittny, JC. Development of the lung. Cell Tissue Res. 2017; 367(3), 427–444.CrossRefGoogle ScholarPubMed
Agassandian, M, Mallampalli, RK. Surfactant phospholipid metabolism. Biochim Biophys Acta. 2013; 1831(3), 612–625.CrossRefGoogle ScholarPubMed
McGillick, EV, Orgeig, S, Allison, BJ, et al. Maternal chronic hypoxia increases expression of genes regulating lung liquid movement and surfactant maturation in male fetuses in late gestation. J Physiol. 2017; 595(13), 4329–4350.CrossRefGoogle ScholarPubMed
Schiller, H, Bensch, K. De novo fatty acid synthesis and elongation of fatty acids by subcellular fractions of lung. J Lipid Res. 1971; 12(2), 248–255.CrossRefGoogle ScholarPubMed
Kasahara, Y, Tuder, RM, Taraseviciene-Stewart, L, et al. Inhibition of VEGF receptors causes lung cell apoptosis and emphysema. J Clin Invest. 2000; 106(11), 1311–1319.CrossRefGoogle ScholarPubMed
Thébaud, B, Ladha, F, Michelakis, ED, et al. Vascular endothelial growth factor gene therapy increases survival, promotes lung angiogenesis, and prevents alveolar damage in hyperoxia-induced lung injury, evidence that angiogenesis participates in alveolarization. Circulation. 2005; 112(16), 2477–2486.CrossRefGoogle ScholarPubMed
Zeng, X, Wert, SE, Federici, R, Peters, KG, Whitsett, JA. VEGF enhances pulmonary vasculogenesis and disrupts lung morphogenesis in vivo. Dev Dyn. 1998; 211(3), 215–227.3.0.CO;2-K>CrossRefGoogle ScholarPubMed
Brown, KRS, England, KM, Goss, KL, Snyder, JM, Acarregui, MJ. VEGF induces airway epithelial cell proliferation in human fetal lung in vitro. Am J Physiol Lung Cell Mol Physiol. 2001; 281(4), L1001–L1010.CrossRefGoogle ScholarPubMed
Compernolle, V, Brusselmans, K, Acker, T, et al. Loss of HIF-2α and inhibition of VEGF impair fetal lung maturation, whereas treatment with VEGF prevents fatal respiratory distress in premature mice. Nat Med. 2002; 8(7), 702–710.CrossRefGoogle ScholarPubMed
Raoul, W, Chailley-Heu, B, Barlier-Mur, A-M, Delacourt, C, Maître, B, Bourbon, JR. Effects of vascular endothelial growth factor on isolated fetal alveolar type II cells. Am J Physiol Lung Cell Mol Physiol. 2004; 286(6), L1293–L1301.CrossRefGoogle ScholarPubMed
Rahimi, N. VEGFR-1 and VEGFR-2: two non-identical twins with a unique physiognomy. Front Biosci. 2006; 11, 818–829.CrossRefGoogle ScholarPubMed
Hiratsuka, S, Minowa, O, Kuno, J, Noda, T, Shibuya, M. Flt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in mice. Proc Natl Acad Sci U S A. 1998; 95(16), 9349–9354.CrossRefGoogle ScholarPubMed
McCarthy, FP, Drewlo, S, English, FA, et al. Evidence implicating peroxisome proliferator-activated receptor-γ in the pathogenesis of preeclampsia. Hypertension. 2011; 58(5), 882–887.CrossRefGoogle ScholarPubMed
Darby, JRT, Varcoe, TJ, Orgeig, S, Morrison, JL. Cardiorespiratory consequences of intrauterine growth restriction, Influence of timing, severity and duration of hypoxaemia. Theriogenology. 2020; 150, 84–95.CrossRefGoogle ScholarPubMed
Morrison, JL. Sheep models of intrauterine growth restriction: Fetal adaptations and consequences. Clin Exp Pharmacol Physiol. 2008; 35(7), 730–743.CrossRefGoogle ScholarPubMed
Dekowski, SA, Snyder, JM. The combined effects of insulin and cortisol on surfactant protein mRNA levels. Pediatr Res. 1995; 38(4), 513–521.CrossRefGoogle ScholarPubMed
Phillips, ID, Simonetta, G, Owens, JA, Robinson, JS, Clarke, IJ, McMillen, IC. Placental restriction alters the functional development of the pituitary-adrenal axis in the sheep fetus during late gestation. Pediatr Res. 1996; 40(6), 861–866.CrossRefGoogle ScholarPubMed
Silva, D, Venihaki, M, Guo, WH, Lopez, MF. Igf2 deficiency results in delayed lung development at the end of gestation. Endocrinology. 2006; 147(12), 5584–5591.CrossRefGoogle ScholarPubMed
Retsch-Bogart, GZ, Moats-Staats, BM, Howard, K, D’Ercole, AJ, Stiles, AD. Cellular localization of messenger RNAs for insulin-like growth factors (IGFs), their receptors and binding proteins during fetal rat lung development. Am J Respir Cell Mol Biol. 1996; 14(1), 61–69.CrossRefGoogle Scholar
Esumi, G, Masumoto, K, Teshiba, R, et al. Effect of insulin-like growth factors on lung development in a nitrofen-induced CDH rat model. Pediatr Surg Int. 2011; 27(2), 187–192.CrossRefGoogle Scholar
Dekowski, SA, Snyder, JM. Insulin regulation of messenger ribonucleic acid for the surfactant-associated proteins in human fetal lung in vitro. Endocrinology. 1992; 131(2), 669–676.Google ScholarPubMed
Rehan, VK, Torday, JS. The lung alveolar lipofibroblast: an evolutionary strategy against neonatal hyperoxic lung injury. Antioxid Redox Signal. 2014; 21(13), 1893–1904.CrossRefGoogle ScholarPubMed
Torday, JS, Rehan, VK. On the evolution of the pulmonary alveolar lipofibroblast. Exp Cell Res. 2016; 340(2), 215–219.CrossRefGoogle ScholarPubMed
Chao, C-M, El Agha, E, Tiozzo, C, Minoo, P, Bellusci, S. A breath of fresh air on the mesenchyme: impact of impaired mesenchymal development on the pathogenesis of bronchopulmonary dysplasia. Front Med. 2015; 2, 27.CrossRefGoogle ScholarPubMed