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Review
. 2023 Mar 1;324(3):L285-L296.
doi: 10.1152/ajplung.00106.2021. Epub 2023 Jan 10.

Complex roles of TGF-β signaling pathways in lung development and bronchopulmonary dysplasia

Rebecca J Calthorpe  1   2 , Caroline Poulter  3 , Alan R Smyth  1   2 , Don Sharkey  4 , Jayesh Bhatt  3 , Gisli Jenkins  5 , Amanda L Tatler  2
Affiliations
Review

Complex roles of TGF-β signaling pathways in lung development and bronchopulmonary dysplasia

Rebecca J Calthorpe et al. Am J Physiol Lung Cell Mol Physiol. .

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.

Keywords: bronchopulmonary dysplasia; transforming growth factor-β.

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Conflict of interest statement

A.R.S has research grants (paid to the University of Nottingham) from Vertex Pharmaceuticals and payment for an advisory board (paid to the University of Nottingham) from Viatris Pharmaceuticals, all outside the current work. A.R.S. has patents issued (Camara M, Williams P, Barrett D, Halliday N, Knox A, Smyth A, Fogarty A, Barr H, Forrester D. Alkyl quinolones as biomarkers of Pseudomonas aeruginosa infection and uses thereof. US2016131648-A1; https://pubchem.ncbi.nlm.nih.gov/patent/US-2016131648-A1). Outside the current work, A.R.S reports participation on a Data Safety Monitoring Board for the North American Cystic Fibrosis Foundation Therapeutic Development Network. R.J.C. was previously supported by a National Institute for Health Research (NIHR) Academic Clinical Fellowship. G.J. reports personal fees and other from Biogen, personal fees from Galapagos, other from Galecto, personal fees and other from GlaxoSmithKline, personal fees from Heptares, personal fees and other from MedImmune, personal fees from Boehringer Ingelheim, personal fees from Pliant, personal fees from Roche/InterMune, personal fees from PharmAkea, personal fees from Bristol Myers Squibb, personal fees from Chiesi, personal fees from Roche/Promedior, other from RedX, other from NuMedii, other from Nordic Biosciences, personal fees from Veracyte, outside the submitted work. G.J. is supported by a National Institute of Health Research Professorship and is a trustee for Action for Pulmonary Fibrosis. A.L.T. reports consulting for biotech.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Risk factors associated with the development of bronchopulmonary dysplasia. [Adapted from Davidson and Berkelhamer (7) under an open access Creative Common CC BY license].
Figure 2.
Figure 2.
Effect of antenatal under and overexpression of TGF-β on lung development.
Figure 3.
Figure 3.
TGF-β expression in response to hyperoxygenation. Initially TGF-β activity decreased in response to hyperoxygenation, however following prolonged exposure, TGF-β activity and downstream signaling increased with increased pSmad2/3.
See this image and copyright information in PMC

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