Direkt zum Inhalt
Merck
  • Vertebrate lonesome kinase modulates the hepatocyte secretome to prevent perivascular liver fibrosis and inflammation.

Vertebrate lonesome kinase modulates the hepatocyte secretome to prevent perivascular liver fibrosis and inflammation.

Journal of cell science (2022-03-17)
Sophia Pantasis, Juliane Friemel, Salome Mirjam Brütsch, Zehan Hu, Sabrina Krautbauer, Gerhard Liebisch, Joern Dengjel, Achim Weber, Sabine Werner, Mattia Renato Bordoli
ZUSAMMENFASSUNG

Vertebrate lonesome kinase (VLK) is the only known extracellular tyrosine kinase, but its physiological functions are largely unknown. We show that VLK is highly expressed in hepatocytes of neonatal mice, but downregulated during adulthood. To determine the role of VLK in liver homeostasis and regeneration, we generated mice with a hepatocyte-specific knockout of the VLK gene (Pkdcc). Cultured progenitor cells established from primary hepatocytes of Pkdcc knockout mice produced a secretome, which promoted their own proliferation in 3D spheroids and proliferation of cultured fibroblasts. In vivo, Pkdcc knockout mice developed liver steatosis with signs of inflammation and perivascular fibrosis upon aging, combined with expansion of liver progenitor cells. In response to chronic CCl4-induced liver injury, the pattern of deposited collagen was significantly altered in these mice. The liver injury marker alpha-fetoprotein (AFP) was increased in the secretome of VLK-deficient cultured progenitor cells and in liver tissues of aged or CCl4-treated knockout mice. These results support a key role for VLK and extracellular protein phosphorylation in liver homeostasis and repair through paracrine control of liver cell function and regulation of appropriate collagen deposition. This article has an associated First Person interview with the first author of the paper.

MATERIALIEN
Produktnummer
Marke
Produktbeschreibung

Roche
Liberase TM Research Grade, medium Thermolysin concentration
SKU
Packungsgröße
Verfügbarkeit
Preis
Menge
Sigma-Aldrich
Y-27632 -dihydrochlorid, ≥98% (HPLC)
SKU
Packungsgröße
Verfügbarkeit
Preis
Menge
Sigma-Aldrich
Monoklonales Anti-β-Aktin in Maus hergestellte Antikörper, clone AC-15, ascites fluid
SKU
Packungsgröße
Verfügbarkeit
Preis
Menge
Sigma-Aldrich
CHIR99021, ≥98% (HPLC)
SKU
Packungsgröße
Verfügbarkeit
Preis
Menge
Sigma-Aldrich
A 83-01, ≥98% (HPLC)
SKU
Packungsgröße
Verfügbarkeit
Preis
Menge
Sigma-Aldrich
Anti-Sox9-Antikörper, Chemicon®, from rabbit
SKU
Packungsgröße
Verfügbarkeit
Preis
Menge
Roche
KAPA2G Fast PCR Kit
SKU
Packungsgröße
Verfügbarkeit
Preis
Menge