Lung developmental arrest caused by PDGF-A deletion: consequences for the adult mouse lung

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Lung developmental arrest caused by PDGF-A deletion : consequences for the adult mouse lung

Gouveia, Maria Leonor Seguardo (author): Uppsala universitet,Vaskulärbiologi

Kraut, Simone (author): Univ Giessen, Justus Liebig Univ Giessen JLUG, Excellence Cluster Cardio Pulm Inst CPI, Giessen, Germany.;Marburg Lung Ctr UGMLC, Giessen, Germany.;German Ctr Lung Res DZL, Giessen, Germany.

Hadzic, Stefan (author): Univ Giessen, Justus Liebig Univ Giessen JLUG, Excellence Cluster Cardio Pulm Inst CPI, Giessen, Germany.;Marburg Lung Ctr UGMLC, Giessen, Germany.;German Ctr Lung Res DZL, Giessen, Germany.

Vazquez-Liebanas, Elisa (author): Uppsala universitet,Vaskulärbiologi

Kojonazarov, Baktybek (author): Univ Giessen, Justus Liebig Univ Giessen JLUG, Excellence Cluster Cardio Pulm Inst CPI, Giessen, Germany.;Marburg Lung Ctr UGMLC, Giessen, Germany.;German Ctr Lung Res DZL, Giessen, Germany.

Wu, Cheng-Yu (author): Univ Giessen, Justus Liebig Univ Giessen JLUG, Excellence Cluster Cardio Pulm Inst CPI, Giessen, Germany.;Marburg Lung Ctr UGMLC, Giessen, Germany.;German Ctr Lung Res DZL, Giessen, Germany.

Veith, Christine (author): Univ Giessen, Justus Liebig Univ Giessen JLUG, Excellence Cluster Cardio Pulm Inst CPI, Giessen, Germany.;Marburg Lung Ctr UGMLC, Giessen, Germany.;German Ctr Lung Res DZL, Giessen, Germany.

He, Liqun (author): Uppsala universitet,Vaskulärbiologi

Mermekkas, Georgics (author): Karolinska Inst, Dept Oncol Pathol, Sci Life Lab, Canc Proteorn Mass Spectrometry, Stockholm, Sweden.

Schermuly, Ralph Theo (author): Univ Giessen, Justus Liebig Univ Giessen JLUG, Excellence Cluster Cardio Pulm Inst CPI, Giessen, Germany.;Marburg Lung Ctr UGMLC, Giessen, Germany.;German Ctr Lung Res DZL, Giessen, Germany.

Weissmann, Norbert (author): Univ Giessen, Justus Liebig Univ Giessen JLUG, Excellence Cluster Cardio Pulm Inst CPI, Giessen, Germany.;Marburg Lung Ctr UGMLC, Giessen, Germany.;German Ctr Lung Res DZL, Giessen, Germany.

Betsholtz, Christer (author): Uppsala universitet,Vaskulärbiologi,Karolinska Inst, Integrated Cardio Metab Ctr, Huddinge, Sweden.

Andrae, Johanna (author): Uppsala universitet,Vaskulärbiologi

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AMER PHYSIOLOGICAL SOC, 2020
2020
English.
In: American Journal of Physiology - Lung cellular and Molecular Physiology. - : AMER PHYSIOLOGICAL SOC. - 1040-0605 .- 1522-1504. ; 318:4, s. L831-L843

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Journal article (peer-reviewed)

Abstract Subject headings

PDGF-A is a key contributor to lung development in mice. Its expression is needed for secondary septation of the alveoli and deletion of the gene leads to abnormally enlarged alveolar air spaces in mice. In humans, the same phenotype is the hallmark of bronchopulmonary dysplasia (BPD), a disease that affects premature babies and may have long lasting consequences in adulthood. So far, the knowledge regarding adult effects of developmental arrest in the lung is limited. This is attributable to few follow-up studies of BPD survivors and lack of good experimental models that could help predict the outcomes of this early age disease for the adult individual. In this study, we used the constitutive lung-specific Pdgfa deletion mouse model to analyze the consequences of developmental lung defects in adult mice. We assessed lung morphology, physiology, cellular content, ECM composition and proteomics data in mature mice, that perinatally exhibited lungs with a BPD-like morphology. Histological and physiological analyses both revealed that enlarged alveolar air spaces remained until adulthood, resulting in higher lung compliance and higher respiratory volume in knockout mice. Still, no or only small differences were seen in cellular, ECM and protein content when comparing knockout and control mice. Taken together, our results indicate that Pdgfa deletion-induced lung developmental arrest has consequences for the adult lung at the morphological and functional level. In addition, these mice can reach adulthood with a BPD-like phenotype, which makes them a robust model to further investigate the pathophysiological progression of the disease and test putative regenerative therapies.

Subject headings

NATURVETENSKAP -- Biologi -- Utvecklingsbiologi (hsv//swe)
NATURAL SCIENCES -- Biological Sciences -- Developmental Biology (hsv//eng)

Keyword

lung
mouse model
PDGF-A

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By the author/editor: Gouveia, Maria L ...; Kraut, Simone; Hadzic, Stefan; Vazquez-Liebanas ...; Kojonazarov, Bak ...; Wu, Cheng-Yu; show more...; Veith, Christine; He, Liqun; Mermekkas, Georg ...; Schermuly, Ralph ...; Weissmann, Norbe ...; Betsholtz, Chris ...; Andrae, Johanna; show less...

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NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Developmental Bi ...

Articles in the publication: American Journal ...

By the university: Uppsala University; Karolinska Institutet

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