Bibliographic Details
| Title: |
Vertebrate lonesome kinase modulates the hepatocyte secretome to prevent perivascular liver fibrosis and inflammation. |
| Authors: |
Pantasis, Sophia1, Friemel, Juliane2, Brütsch, Salome Mirjam1, Zehan Hu3, Krautbauer, Sabrina4, Liebisch, Gerhard4, Dengjel, Joern3, Weber, Achim2, Werner, Sabine1 sabine.werner@biol.ethz.ch, Bordoli, Mattia Renato1 mattia.bordoli@novartis.com |
| Source: |
Journal of Cell Science. Apr2022, Vol. 135 Issue 7, p1-1. 1p. |
| Subject Terms: |
*HEPATIC fibrosis, *LIVER cells, *KNOCKOUT mice, *CELLULAR control mechanisms, *PROGENITOR cells, *CELL physiology |
| 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 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. [ABSTRACT FROM AUTHOR] |
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| Database: |
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