Overexpression of Spock2 in mice leads to altered lung alveolar development and worsens lesions induced by hyperoxia.

Autor:	Hadchouel A; Service de Pneumologie et d'Allergologie Pédiatriques, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique - Hôpitaux de Paris, Paris, France.; Equipe 4, U955, Institut National de la Santé et de la Recherche Médicale, Créteil, France.; Université de Paris, Paris, France., Franco-Montoya ML; Service de Pneumologie et d'Allergologie Pédiatriques, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique - Hôpitaux de Paris, Paris, France., Guerin S; Service de Pneumologie et d'Allergologie Pédiatriques, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique - Hôpitaux de Paris, Paris, France.; Equipe 4, U955, Institut National de la Santé et de la Recherche Médicale, Créteil, France., Do Cruzeiro M; Homologous Recombination, Cochin Institute, Université de Paris, Paris, France., Lhuillier M; U1151, Institut National de la Santé et de la Recherche Médicale, Institut Necker-Enfants Malades, Université de Paris, Paris, France., Ribeiro Baptista B; Equipe 4, U955, Institut National de la Santé et de la Recherche Médicale, Créteil, France., Boyer L; Equipe 4, U955, Institut National de la Santé et de la Recherche Médicale, Créteil, France., Lanone S; Equipe 4, U955, Institut National de la Santé et de la Recherche Médicale, Créteil, France., Delacourt C; Service de Pneumologie et d'Allergologie Pédiatriques, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique - Hôpitaux de Paris, Paris, France.; Equipe 4, U955, Institut National de la Santé et de la Recherche Médicale, Créteil, France.; Université de Paris, Paris, France.
Jazyk:	angličtina
Zdroj:	American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2020 Jul 01; Vol. 319 (1), pp. L71-L81. Date of Electronic Publication: 2020 May 06.
DOI:	10.1152/ajplung.00191.2019
Abstrakt:	SPARC/osteonectin, cwcv and kazal-like domains proteoglycan 2 ( SPOCK2 ) was previously associated with genetic susceptibility to bronchopulmonary dysplasia in a French population of very preterm neonates. Its expression increases during lung development and is increased after exposure of rat pups to hyperoxia compared with controls bred in room air. To further investigate the role of SPOCK2 during lung development, we designed two mouse models, one that uses a specific anti-Spock2 antibody and one that reproduces the hyperoxia-induced Spock2 expression with a transgenic mouse model resulting in a conditional and lung-targeted overexpression of Spock2 . When mice were bred under hyperoxic conditions, treatment with anti-Spock2 antibodies significantly improved alveolarization. Lung overexpression of Spock2 altered alveolar development in pups bred in room air and worsened hyperoxia-induced lesions. Neither treatment with anti-Spock2 antibody nor overexpression of Spock2 was associated with abnormal activation of matrix metalloproteinase-2. These two models did not alter the expression of known players in alveolar development. This study brings strong arguments for the deleterious role of SPOCK2 on lung alveolar development especially after lung injury, suggesting its role in bronchopulmonary dysplasia susceptibility. These effects are not mediated by a deregulation in metalloproteases activity and in expression of factors essential to normal alveolarization. The balance between types 1 and 2 epithelial alveolar cells may be involved.
Databáze:	MEDLINE
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