Details der Publikation - Mesenchyme-derived vertebrate lonesome kinase controls lung organogenesis by altering the matrisome

Mesenchyme-derived vertebrate lonesome kinase controls lung organogenesis by altering the matrisome

Abstract Vertebrate lonesome kinase (VLK) is the only known secreted tyrosine kinase and responsible for the phosphorylation of a broad range of secretory pathway-resident and extracellular matrix proteins. However, its cell-type specific functions in vivo are still largely unknown. Therefore, we generated mice lacking the VLK gene (protein kinase domain containing, cytoplasmic (Pkdcc)) in mesenchymal cells. Most of the homozygous mice died shortly after birth, most likely as a consequence of their lung abnormalities and consequent respiratory failure. E18.5 embryonic lungs showed a reduction of alveolar type II cells, smaller bronchi, and an increased lung tissue density. Global mass spectrometry-based quantitative proteomics identified 97 proteins with significantly and at least 1.5-fold differential abundance between genotypes. Twenty-five of these had been assigned to the extracellular region and 15 to the mouse matrisome. Specifically, fibromodulin and matrilin-4, which are involved in extracellular matrix organization, were significantly more abundant in lungs from Pkdcc knockout embryos. These results support a role for mesenchyme-derived VLK in lung development through regulation of matrix dynamics and the resulting modulation of alveolar epithelial cell differentiation..

Medienart:	E-Artikel

Erscheinungsjahr:	2023
Erschienen:	2023

Enthalten in:	Zur Gesamtaufnahme - volume:80
Enthalten in:	Cellular and molecular life sciences - 80(2023), 4 vom: 15. März

Sprache:	Englisch

Beteiligte Personen:	Brütsch, Salome M. [VerfasserIn] Madzharova, Elizabeta [VerfasserIn] Pantasis, Sophia [VerfasserIn] Wüstemann, Till [VerfasserIn] Gurri, Selina [VerfasserIn] Steenbock, Heiko [VerfasserIn] Gazdhar, Amiq [VerfasserIn] Kuhn, Gisela [VerfasserIn] Angel, Peter [VerfasserIn] Bellusci, Saverio [VerfasserIn] Brinckmann, Jürgen [VerfasserIn] auf dem Keller, Ulrich [VerfasserIn] Werner, Sabine [VerfasserIn] Bordoli, Mattia R. [VerfasserIn]

Links:	Volltext [kostenfrei]

Themen:	Collagen Lung organogenesis Proteomics Skull

Anmerkungen:	© The Author(s) 2023

doi:	10.1007/s00018-023-04735-6

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	OLC2134488123

Internformat


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520			\|a Abstract Vertebrate lonesome kinase (VLK) is the only known secreted tyrosine kinase and responsible for the phosphorylation of a broad range of secretory pathway-resident and extracellular matrix proteins. However, its cell-type specific functions in vivo are still largely unknown. Therefore, we generated mice lacking the VLK gene (protein kinase domain containing, cytoplasmic (Pkdcc)) in mesenchymal cells. Most of the homozygous mice died shortly after birth, most likely as a consequence of their lung abnormalities and consequent respiratory failure. E18.5 embryonic lungs showed a reduction of alveolar type II cells, smaller bronchi, and an increased lung tissue density. Global mass spectrometry-based quantitative proteomics identified 97 proteins with significantly and at least 1.5-fold differential abundance between genotypes. Twenty-five of these had been assigned to the extracellular region and 15 to the mouse matrisome. Specifically, fibromodulin and matrilin-4, which are involved in extracellular matrix organization, were significantly more abundant in lungs from Pkdcc knockout embryos. These results support a role for mesenchyme-derived VLK in lung development through regulation of matrix dynamics and the resulting modulation of alveolar epithelial cell differentiation.
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700	1		\|a Madzharova, Elizabeta \|4 aut
700	1		\|a Pantasis, Sophia \|4 aut
700	1		\|a Wüstemann, Till \|4 aut
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700	1		\|a Steenbock, Heiko \|4 aut
700	1		\|a Gazdhar, Amiq \|4 aut
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700	1		\|a Angel, Peter \|4 aut
700	1		\|a Bellusci, Saverio \|4 aut
700	1		\|a Brinckmann, Jürgen \|4 aut
700	1		\|a auf dem Keller, Ulrich \|4 aut
700	1		\|a Werner, Sabine \|0 (orcid)0000-0001-7397-8710 \|4 aut
700	1		\|a Bordoli, Mattia R. \|4 aut
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Mesenchyme-derived vertebrate lonesome kinase controls lung organogenesis by altering the matrisome

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