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

Abstract : 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.
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Contributor : Sophie Lanone <>
Submitted on : Monday, August 24, 2020 - 2:26:33 PM
Last modification on : Thursday, August 27, 2020 - 3:25:46 AM

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Alice Hadchouel, Marie-Laure Franco-Montoya, Sophie Guérin, Marcio Do Cruzeiro, Mickael Lhuillier, et al.. Overexpression of Spock2 in mice leads to altered lung alveolar development and worsens lesions induced by hyperoxia: over expression of Spock2 and altered lung development. American Journal of Physiology - Lung Cellular and Molecular Physiology, American Physiological Society, 2020, 319 (1), pp.L71-L81. ⟨10.1152/ajplung.00191.2019⟩. ⟨inserm-02920089⟩

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