Bronchopulmonary dysplasia (BPD) is a respiratory complication characterized by abnormal alveolar development in premature infants. Geranylgeranylacetone (GGA) can induce heat shock protein (HSP) 70, which has cytoprotective effects against various stressors. Here, we investigated whether GGA protected neonatal lungs from hyperoxic stress in a murine BPD model, and measured the serum HSP70 levels in preterm humans treated with oxygen.
Newborn mice were exposed to >90% oxygen and administered GGA or vehicle alone orally on days 1, 2, and 3 of life. At 2 days of age, HSP70 expression in the lung was determined by western blotting. At 8 days of age, the lungs were processed for histological analysis. Radial alveolar count (RAC) and mean linear intercept (MLI) were measured as parameters of alveolarization. Apoptosis was evaluated by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method and cleaved caspase-3 immunohistochemistry. Serum HSP70 levels in preterm humans treated with oxygen were measured by enzyme-linked immunosorbent assay.
GGA administration enhanced the HSP70 expression to two-fold compared with normoxia-exposed and vehicle-treated mice. Hyperoxia reduced HSP70 expression, whereas GGA abrogated the effects. Hyperoxia-exposed mice exhibited more apoptotic cells in lung parenchyma and a more simplified alveolar structure with less RAC and larger MLI than normoxia-exposed mice. GGA suppressed the increase in apoptotic cells and the structural changes of the lungs induced by hyperoxia. Serum HSP70 levels of preterm human infants gradually decreased with age.
GGA may attenuate hyperoxic injury in neonatal lungs and thereby may prevent the development of BPD.
Sliva DM, Nardiello C, Pozarska A et al (2015) Recent advances in the mechanisms of lung alveolarization and the pathogenesis of bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol 309:L1239–L1272
Wong HR, Menendez IY, Ryan MA et al (1998) Increased expression of heat shock protein-70 protects A549 cells against hyperoxia. Am J Physiol 275:L836–L841 PubMed
Yi Zhang, Zang X, Shan P et al (2013) A protective HSP70-TLR4 pathway in lethal oxidant lung injury. J Immunol 191:1393–1403 CrossRef
Tanaka K, Tanaka Y, Namba T et al (2010) Heat shock protein 70 protects against bleomycin-induced pulmonary fibrosis in mice. Biolchem Pharmacol 80:920–931 CrossRef
Thomas PC, William MT (1982) The radial alveolar count method of Emery and Mithal: a reappraisal 1- postnatal lung growth. Thorax 37:572–579 CrossRef
Vivek B, Jen-Ruey T, Anne M et al (2003) Mild hypoxia impairs alveolarization in the endothelial nitric oxide synthase-deficient mouse. Am J Physiol Lung Cell Mol Physiol 284:L964–L971 CrossRef
- Treatment with Geranylgeranylacetone Induces Heat Shock Protein 70 and Attenuates Neonatal Hyperoxic Lung Injury in a Model of Bronchopulmonary Dysplasia
- Springer US
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