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Protective effect of keratinocyte growth factor against lung abnormalities associated with hyperoxia in prematurely
1Pulmonary Division, University of Miami School of Medicine, Miami, FL 33101, USA. lfrank@med.miami.edu
Insights
Keratinocyte growth factor (KGF) treatment improved survival in a rat model of bronchopulmonary dysplasia (BPD) induced by hyperoxia. KGF also prevented pulmonary hypertension, but not impaired alveoli formation or fibrosis.
Area of Science:
- Neonatal Physiology
- Pulmonary Medicine
- Developmental Biology
Background:
- Bronchopulmonary dysplasia (BPD) is a serious complication in premature infants exposed to hyperoxia.
- Early life hyperoxia can lead to severe cardio-pulmonary issues.
- Identifying protective factors is crucial for managing BPD.
Purpose of the Study:
- To investigate the protective effects of keratinocyte growth factor (KGF) against hyperoxia-induced BPD complications in a premature rat model.
- To assess KGF's impact on lethality, alveoli development, pulmonary fibrosis, and pulmonary hypertension.
Main Methods:
- A prematurely born rat model was exposed to hyperoxia.
- Animals received either KGF treatment or saline control.
- Survival rates, alveoli formation, pulmonary fibrosis, and right ventricular hypertrophy were evaluated.
Main Results:
- KGF significantly improved survival rates in the hyperoxia group (78% vs. 44%).
- KGF did not protect against inhibited alveoli formation or early pulmonary fibrosis.
- KGF significantly prevented pulmonary hypertension, evidenced by reduced right ventricular hypertrophy (+3% vs. +35% increase).
Conclusions:
- KGF demonstrates significant protective effects against hyperoxic lethality and pulmonary hypertension in a premature rat model of BPD.
- KGF does not prevent all hyperoxia-induced lung injuries, specifically impaired alveoli development and fibrosis.
- KGF holds potential as a therapeutic agent for specific cardio-pulmonary complications associated with BPD.
Abstract:
We used a prematurely born rat/hyperoxia model of bronchopulmonary dysplasia (BPD) to test whether keratinocyte growth factor (KGF) treatment would protect against the development of several serious (cardio-)pulmonary complications of early life exposure to hyperoxia. KGF significantly protected against hyperoxic lethality (13-day survival rate = 50/64 (78%) for the O(2)-KGF vs. 29/66 (44%) for the O(2)-saline group, p < 0.001). Although KGF failed to protect against hyperoxic inhibition of normal postnatal alveoli formation and early pulmonary fibrosis, KGF consistently had a significant protective/preventive effect against the development of pulmonary hypertension during hyperoxia as reflected in comparative right ventricular hypertrophy: mean increase = +35% above normal for the O(2)-saline group vs. +3% for the O(2)-KGF premature rat group (p < 0.01).
