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Recombinant Human Elafin Promotes Alveologenesis in Newborn Mice Exposed to Chronic Hyperoxia

Recombinant Human Elafin Promotes Alveologenesis in Newborn Mice Exposed to Chronic Hyperoxia

Wenli Han, Xiaomei Li, Han Zhang, Benli Yu, Chunbao Guo, Chun Deng

Int J Biochem Cell Biol. 2017 Nov;92:173-182.

PMID: 28802561

Abstract:

Background/aims:
Elastase inhibitors reverse elastin degradation and abnormal alveologenesis and attenuate the lung structural abnormalities induced by mechanical ventilation with O2-rich gas. The potential of these molecules to improve endothelial function and to ameliorate severe bronchopulmonary dysplasia (BPD) during lung development is not yet understood. We sought to determine whether the intratracheal treatment of newborn mice with the elastase inhibitor elafin would prevent hyperoxia-induced lung elastin degradation and the cascade of events that cause abnormal alveologenesis.
Methods:
Newborn mice were exposed to 85% O2 for 3, 7, 14 or 21days. Recombinant human elafin was administered by intratracheal instillation from the first day every two days for 20days. We next used morphometric analyses, quantitative RT-PCR, immunostaining, Western blotting, and ELISA methods to assess the key variables involved in elastogenesis disruption and the potential signaling pathways noted below in recombinant human elafin-treated mouse pups that had been exposed to 85% O2.
Results:
We found that impaired alveolar development and aberrant elastin production were associated with elevations in whole lung elastase levels in 85% O2-exposed lungs. Elafin attenuated the structural disintegration that developed in the hyperoxia-damaged lungs. Furthermore, elafin prevented the elastin degradation, neutrophil influx, activation of TGF-β1 and apoptosis caused by 85% O2 exposure.
Conclusions:
Pulmonary elastase plays an important role in disrupting elastogenesis during O2-induced damage, which is the result of a pulmonary inflammatory response. Elafin prevents these changes by inhibiting elastase and the TGF-β1 signalling cascade and may be a new therapeutic target for preventing O2-induced lung injury in neonates.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4241118	Elafin human			Price

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