Complex Roles of TGF-β Signaling Pathways in Lung Development and Bronchopulmonary Dysplasia

Overview

Journal Am J Physiol Lung Cell Mol Physiol

Publisher American Physiological Society

Specialties Cell Biology
Molecular Biology
Physiology
Pulmonary Medicine

Date 2023 Jan 10

PMID 36625900

Authors

Rebecca J Calthorpe

Caroline Poulter

Alan R Smyth

Don Sharkey

Jayesh Bhatt

Gisli Jenkins

Amanda L Tatler

Affiliations

Soon will be listed here.

Abstract

As survival of extremely preterm infants continues to improve, there is also an associated increase in bronchopulmonary dysplasia (BPD), one of the most significant complications of preterm birth. BPD development is multifactorial resulting from exposure to multiple antenatal and postnatal stressors. BPD has both short-term health implications and long-term sequelae including increased respiratory, cardiovascular, and neurological morbidity. Transforming growth factor β (TGF-β) is an important signaling pathway in lung development, organ injury, and fibrosis and is implicated in the development of BPD. This review provides a detailed account on the role of TGF-β in antenatal and postnatal lung development, the effect of known risk factors for BPD on the TGF-β signaling pathway, and how medications currently in use or under development, for the prevention or treatment of BPD, affect TGF-β signaling.

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References

Majnemer A, Riley P, Shevell M, Birnbaum R, Greenstone H, Coates A . Severe bronchopulmonary dysplasia increases risk for later neurological and motor sequelae in preterm survivors. Dev Med Child Neurol. 2000; 42(1):53-60. DOI: 10.1017/s001216220000013x. View

Abman S, Bancalari E, Jobe A . The Evolution of Bronchopulmonary Dysplasia after 50 Years. Am J Respir Crit Care Med. 2017; 195(4):421-424. DOI: 10.1164/rccm.201611-2386ED. View

Londhe V, Maisonet T, Lopez B, Shin B, Huynh J, Devaskar S . Retinoic acid rescues alveolar hypoplasia in the calorie-restricted developing rat lung. Am J Respir Cell Mol Biol. 2012; 48(2):179-87. PMC: 3604067. DOI: 10.1165/rcmb.2012-0229OC. View

Goodwin A, John A, Joseph C, Habgood A, Tatler A, Susztak K . Stretch regulates alveologenesis and homeostasis via mesenchymal Gαq/11-mediated TGFβ2 activation. Development. 2023; 150(9). PMC: 10259661. DOI: 10.1242/dev.201046. View

Ehrhardt H, Pritzke T, Oak P, Kossert M, Biebach L, Forster K . Absence of TNF-α enhances inflammatory response in the newborn lung undergoing mechanical ventilation. Am J Physiol Lung Cell Mol Physiol. 2016; 310(10):L909-18. PMC: 4896101. DOI: 10.1152/ajplung.00367.2015. View

Gitto E, Pellegrino S, DArrigo S, Barberi I, Reiter R . Oxidative stress in resuscitation and in ventilation of newborns. Eur Respir J. 2009; 34(6):1461-9. DOI: 10.1183/09031936.00032809. View

Teichert-Kuliszewska K, Kutryk M, Kuliszewski M, Karoubi G, Courtman D, Zucco L . Bone morphogenetic protein receptor-2 signaling promotes pulmonary arterial endothelial cell survival: implications for loss-of-function mutations in the pathogenesis of pulmonary hypertension. Circ Res. 2005; 98(2):209-17. DOI: 10.1161/01.RES.0000200180.01710.e6. View

Onland W, De Jaegere A, Offringa M, van Kaam A . Systemic corticosteroid regimens for prevention of bronchopulmonary dysplasia in preterm infants. Cochrane Database Syst Rev. 2017; 1:CD010941. PMC: 6464844. DOI: 10.1002/14651858.CD010941.pub2. View

Geng Y, Dong Y, Yu M, Zhang L, Yan X, Sun J . Follistatin-like 1 (Fstl1) is a bone morphogenetic protein (BMP) 4 signaling antagonist in controlling mouse lung development. Proc Natl Acad Sci U S A. 2011; 108(17):7058-63. PMC: 3084141. DOI: 10.1073/pnas.1007293108. View

10.

Bonikos D, Bensch K, NORTHWAY Jr W . Oxygen toxicity in the newborn. The effect of chronic continuous 100 percent oxygen exposure on the lungs of newborn mice. Am J Pathol. 1976; 85(3):623-50. PMC: 2032655. View

11.

John A, Wilson M, Habgood A, Porte J, Tatler A, Stavrou A . Loss of epithelial Gq and G11 signaling inhibits TGFβ production but promotes IL-33-mediated macrophage polarization and emphysema. Sci Signal. 2016; 9(451):ra104. DOI: 10.1126/scisignal.aad5568. View

12.

Shahzad T, Radajewski S, Chao C, Bellusci S, Ehrhardt H . Pathogenesis of bronchopulmonary dysplasia: when inflammation meets organ development. Mol Cell Pediatr. 2016; 3(1):23. PMC: 4927524. DOI: 10.1186/s40348-016-0051-9. View

13.

Kim S, Henen M, Hinck A . Structural biology of betaglycan and endoglin, membrane-bound co-receptors of the TGF-beta family. Exp Biol Med (Maywood). 2019; 244(17):1547-1558. PMC: 6920675. DOI: 10.1177/1535370219881160. View

14.

Reiss I, Landmann E, Heckmann M, Misselwitz B, Gortner L . Increased risk of bronchopulmonary dysplasia and increased mortality in very preterm infants being small for gestational age. Arch Gynecol Obstet. 2003; 269(1):40-4. DOI: 10.1007/s00404-003-0486-9. View

15.

Tatler A, Barnes J, Habgood A, Goodwin A, McAnulty R, Jenkins G . Caffeine inhibits TGFβ activation in epithelial cells, interrupts fibroblast responses to TGFβ, and reduces established fibrosis in ex vivo precision-cut lung slices. Thorax. 2016; 71(6):565-7. PMC: 4893128. DOI: 10.1136/thoraxjnl-2015-208215. View

16.

Chen F, Cao Y, Qian J, Shao F, Niederreither K, Cardoso W . A retinoic acid-dependent network in the foregut controls formation of the mouse lung primordium. J Clin Invest. 2010; 120(6):2040-8. PMC: 2877937. DOI: 10.1172/JCI40253. View

17.

Baud O, Maury L, Lebail F, Ramful D, El Moussawi F, Nicaise C . Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre, randomised trial. Lancet. 2016; 387(10030):1827-36. DOI: 10.1016/S0140-6736(16)00202-6. View

18.

Li M, Flavell R . TGF-beta: a master of all T cell trades. Cell. 2008; 134(3):392-404. PMC: 3677783. DOI: 10.1016/j.cell.2008.07.025. View

19.

NORTHWAY Jr W, ROSAN R, Porter D . Pulmonary disease following respirator therapy of hyaline-membrane disease. Bronchopulmonary dysplasia. N Engl J Med. 1967; 276(7):357-68. DOI: 10.1056/NEJM196702162760701. View

20.

Fehrholz M, Speer C, Kunzmann S . Caffeine and rolipram affect Smad signalling and TGF-β1 stimulated CTGF and transgelin expression in lung epithelial cells. PLoS One. 2014; 9(5):e97357. PMC: 4020861. DOI: 10.1371/journal.pone.0097357. View