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

Brütsch, Salome M; Madzharova, Elizabeta; Pantasis, Sophia; Wüstemann, Till; Gurri, Selina; Steenbock, Heiko; Gazdhar, Amiq; Kuhn, Gisela; Angel, Peter; Bellusci, Saverio; Brinckmann, Jürgen; Auf dem Keller, Ulrich; Werner, Sabine; Bordoli, Mattia R (2023). Mesenchyme-derived vertebrate lonesome kinase controls lung organogenesis by altering the matrisome. Cellular and molecular life sciences : CMLS, 80(4), p. 89. Springer 10.1007/s00018-023-04735-6

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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.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Pneumologie (Erwachsene)
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology

UniBE Contributor:

Gazdhar, Amiq


600 Technology > 610 Medicine & health








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Date Deposited:

16 Mar 2023 10:15

Last Modified:

19 Mar 2023 02:15

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Uncontrolled Keywords:

Collagen Lung organogenesis Pkdcc Proteomics Skull




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