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Updated: Jun 3, 2026
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Published on: August 4, 2021
rhKGF stimulates lung surfactant production in neonatal rats in vivo
Jens Gesche1, Heinz Fehrenbach, Roland Koslowski
1Faculty of Medicine, Department of Neonatology, Eberhard-Karls-University, Tübingen, Germany.
Insights
Keratinocyte growth factor (KGF) enhances surfactant production in preterm infants without harmful side effects, unlike betamethasone. This suggests KGF as a potential non-catabolic therapeutic for neonatal lung injury.
Area of Science:
- Neonatal physiology
- Pulmonary medicine
- Developmental biology
Background:
- Bronchopulmonary dysplasia (BPD) and surfactant deficiency are critical issues in preterm infants.
- Glucocorticoids treat these conditions but cause detrimental catabolic side effects.
- Keratinocyte growth factor (KGF) promotes surfactant production and epithelial protection, showing promise for neonatal lung health.
Purpose of the Study:
- To evaluate the efficacy of recombinant human KGF (rhKGF) and betamethasone (BM) in a neonatal rat model.
- To compare the effects of rhKGF, BM, and their combination on surfactant production, lung tissue, and animal growth.
- To assess the impact on pneumocyte proliferation and surfactant protein expression.
Main Methods:
- Neonatal rats were treated with rhKGF, BM, or both for 48 hours.
- Measurements included body weight, surfactant, and tissue phosphatidylcholines (PC) at postnatal days 3, 7, 15, and 21.
- Pneumocyte proliferation, surfactant protein (SP) expression, and SP-B/C in lung lavage fluid were analyzed.
Main Results:
- All treatments increased secreted surfactant PC; rhKGF did not compromise growth, unlike BM.
- rhKGF was more effective in male rats at day 3.
- BM inhibited pneumocyte proliferation and shifted PC balance, while rhKGF increased surfactant PC without negative effects on other PC species.
Conclusions:
- rhKGF effectively increases surfactant PC levels without the catabolic side effects of betamethasone.
- rhKGF demonstrates potential as a non-catabolic therapeutic for neonatal lung injury.
- Further research is warranted to explore rhKGF's mechanisms and efficacy in clinical settings.
Abstract:
Surfactant deficiency and bronchopulmonary dysplasia (BPD), major obstacles in preterm infants, are addressed with pre- and postnatal glucocorticoids which also evoke harmful catabolic side-effects. Keratinocyte growth factor (KGF) accelerates surfactant production in fetal type II pneumocytes (PN-II), protects epithelia from injury and is deficient in lungs developing BPD, highlighting its potential efficacy in neonates. Neonatal rats were treated with recombinant human (rh)KGF, betamethasone, or their combination for 48 hr prior to sacrifice after which body weight, surfactant, and tissue phosphatidylcholines (PC) were investigated at postnatal d3, d7, d15, and d21. Pneumocyte proliferation, surfactant protein (SP) expression and SP-B/C in lung lavage fluid (LLF) were also determined at d7 and d21 to identify broader surfactant changes occurring at the beginning and end of the initial alveolarization phase. While all treatments increased secreted surfactant PC, BM compromised animal growth whereas rhKGF did not. At d3 rhKGF was more effective in male compared to female rats. Single treatments became less effective towards d21. Neither treatment altered PC composition in LLF. BM inhibited PN-II proliferation and increased surfactant PCs at the expense of tissue PCs. rhKGF however increased surfactant PCs without decreasing other PC species. Whereas SP-B/C gene expression was induced by all treatments, the changes in secreted SP-B/C mirrored those observed for surfactant PC. Our results encourage investigation of the mechanisms by which rhKGF improves surfactant homoeostasis, and detailed examination of its efficacy in neonatal lung injury models with a view to implementing it as a non-catabolic surfactant-increasing therapeutic in neonatal intensive care.
