Pantasis, Sophia and Friemel, Juliane and Bruetsch, Salome Mirjam and Hu, Zehan and Krautbauer, Sabrina and Liebisch, Gerhard and Dengjel, Joern and Weber, Achim and Werner, Sabine and Bordoli, Mattia Renato (2022) Vertebrate Ionesome kinase modulates the hepatocyte secretome to prevent perivascular liver fibrosis and inflammation. JOURNAL OF CELL SCIENCE, 135 (7): jcs259243. ISSN 0021-9533, 1477-9137
Full text not available from this repository. (Request a copy)Abstract
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 CCI4-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 CCI4-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROGENITOR CELLS; BILE-ACIDS; HOMEOSTASIS; VLK; QUANTIFICATION; MECHANISM; BACTERIA; INJURY; GENE; Collagen; Fibrosis; Liver; Secreted kinase; VLK; Pkdcc |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Feb 2024 14:26 |
| Last Modified: | 29 Feb 2024 14:26 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58245 |
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