TLR3 promotes hepatocyte proliferation after partial hepatectomy by stimulating uPA expression and the release of tissue-bound HGF
| Autor: | Felicitas Altmayr, Miao Lu, Bernhard Holzmann, Melanie Laschinger, Christian Stöß, D. Hartmann, Baocai Wang, Norbert Hüser |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male viruses Organogenesis chemical and pharmacologic phenomena Biochemistry Extracellular matrix 03 medical and health sciences Mice 0302 clinical medicine Immune system Downregulation and upregulation Genetics medicine Hepatic Stellate Cells Animals Hepatectomy Molecular Biology Cell Proliferation Chemistry Hepatocyte Growth Factor virus diseases hemic and immune systems Urokinase-Type Plasminogen Activator In vitro Liver regeneration Cell biology ddc Extracellular Matrix Liver Regeneration Toll-Like Receptor 3 Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Liver Hepatocyte TLR3 Hepatic stellate cell Hepatocytes 030217 neurology & neurosurgery Biotechnology |
| Zdroj: | FASEB journal : official publication of the Federation of American Societies for Experimental BiologyREFERENCES. 34(8) |
| ISSN: | 1530-6860 |
| Popis: | TLR3 is implicated in anti-viral immune responses, but may also act as a sensor of tissue damage in the absence of infection. Here, we provide evidence for an essential role of TLR3 in liver regeneration after an acute loss of tissue due to partial hepatectomy. Mice lacking TLR3 had a severe and sustained defect in the restoration of liver tissue with reduced liver-to-body weight ratios even after an extended recovery period of 2 weeks. Hepatocyte cell cycle progression into S phase was impaired in TLR3-deficient mice. Mechanistic analyses revealed that TLR3-deficient mice had markedly reduced systemic levels of active HGF, but had increased amounts of inactive tissue-bound HGF. Importantly, expression of uPA, which orchestrates the processing and release of HGF from the hepatic extracellular matrix, was reduced in regenerating livers of TLR3-deficient mice. In addition, expression of the HGF maturation factor HGFAC was transiently diminished in TLR3-deficient mice. In vitro, engagement of TLR3 directly stimulated expression of uPA by hepatic stellate cells. Thus, TLR3 supports liver regeneration through upregulation of uPA, which promotes the release of preformed HGF from extracellular matrix stores. |
| Databáze: | OpenAIRE |
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