Universität zu Köln

Will, Johannes P., Hirani, Dharmesh, Thielen, Florian, Klein, Fabian, Vohlen, Christina, Dinger, Katharina, Doetsch, Joerg and Alcazar, Miguel A. Alejandrez (2019). Strain-dependent effects on lung structure, matrix remodeling, and Stat3/Smad2 signaling in C57BL/6N and C57BL/6J mice after neonatal hyperoxia. Am. J. Physiol.-Regul. Integr. Comp. Physiol., 317 (1). S. R169 - 13. BETHESDA: AMER PHYSIOLOGICAL SOC. ISSN 1522-1490

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Abstract

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of preterm infants, characterized by lung growth arrest and matrix remodeling. Various animal models provide mechanistic insights in the pathogenesis of BPD. Since there is increasing evidence that genetic susceptibility modifies the response to lung injury, we investigated strain-dependent effects in hyperoxia (HYX)-induced lung injury of newborn mice. To this end, we exposed newborn C57BL/6N and C57BL/6J mice to 85% O-2 (HYX) or normoxia (NOX; 21% O-2) for 28 days, followed by lung excision for histological and molecular measurements. BL/6J-NOX mice exhibited a lower body and lung weight than BL/6N-NOX mice; hyperoxia reduced body weight in both strains and increased lung weight only in BL/6J-HYX mice. Quantitative histomorphometric analyses revealed reduced alveolar formation in lungs of both strains after HYX, but the effect was greater in BL/6J-HYX mice than BL/6N-HYX mice. Septal thickness was lower in BL/6J-NOX mice than BL/6N-NOX mice but increased in both strains after HYX. Elastic fiber density was significantly greater in BL/6J-HYX mice than BL/6N-HYX mice. Lungs of BL/6J-HYX mice were protected from changes in gene expression of fibrillin-1, fibrillin-2, fibulin-4, fibulin-5, and surfactant proteins seen in BL/6N-HYX mice. Finally, Stat3 was activated by HYX in both strains; in contrast, activation of Smad2 was markedly greater in lungs of BL/6N mice than BL/6J mice after HYX. In summary, we demonstrate strain-dependent differences in lung structure and matrix, alveolar epithelial cell markers, and Smad2 (transforming growth factor beta) signaling in neonatal HYX-induced lung injury. Strain-dependent effects and genetic susceptibility need be taken into consideration for reproducibility and reliability of results in animal models.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Will, Johannes P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hirani, Dharmesh UNSPECIFIED UNSPECIFIED UNSPECIFIED Thielen, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein, Fabian UNSPECIFIED UNSPECIFIED UNSPECIFIED Vohlen, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Dinger, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Doetsch, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Alcazar, Miguel A. Alejandrez UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-136118
DOI:	10.1152/ajpregu.00286.2018
Journal or Publication Title:	Am. J. Physiol.-Regul. Integr. Comp. Physiol.
Volume:	317
Number:	1
Page Range:	S. R169 - 13
Date:	2019
Publisher:	AMER PHYSIOLOGICAL SOC
Place of Publication:	BETHESDA
ISSN:	1522-1490
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BRONCHOPULMONARY DYSPLASIA.; QUANTITATIVE MICROSCOPY; ANIMAL-MODELS; MOUSE MODEL; DISEASE; RESPONSES; INFLAMMATION; PATHOGENESIS; SENSITIVITY; METASTASIS Multiple languages Physiology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13611