Chemerin-156 is the Active Isoform in Human Hepatic Stellate Cells
| Autor: | Spirk, Marlen, Zimny, Sebastian, Neumann, Maximilian, McMullen, Nichole, Sinal, Christopher J., Buechler, Christa |
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| Rok vydání: | 2020 |
| Předmět: |
ddc:610
IL-6 Galectin-3 Proliferation Tango Assay CMKLR1 Galectin 3 610 Medizin Actins Article Cell Line Receptors G-Protein-Coupled lcsh:Chemistry lcsh:Biology (General) lcsh:QD1-999 Hepatic Stellate Cells Humans Protein Isoforms Receptors Chemokine Chemokines lcsh:QH301-705.5 Cells Cultured Cell Proliferation |
| Zdroj: | International Journal of Molecular Sciences, Vol 21, Iss 7555, p 7555 (2020) International Journal of Molecular Sciences Volume 21 Issue 20 |
| DOI: | 10.5283/epub.43998 |
| Popis: | The chemokine chemerin exists as C-terminally processed isoforms whose biological functions are mostly unknown. A highly active human chemerin variant (huChem-157) was protective in experimental hepatocellular carcinoma (HCC) models. Hepatic stellate cells (HSCs) are central mediators of hepatic fibrogenesis and carcinogenesis and express the chemerin receptors chemokine-like receptor 1 (CMKLR1) and G protein-coupled receptor 1 (GPR1). Here we aimed to analyse the effect of chemerin isoforms on the viability, proliferation and secretome of the human HSC cell line LX-2. Therefore, huChem-157, 156 and 155 were over-expressed in LX-2 cells, which have low endogenous chemerin levels. HuChem-157 produced in LX-2 cells activated CMKLR1 and GPR1, and huChem-156 modestly induced GPR1 signaling. HuChem-155 is an inactive chemerin variant. Chemerin isoforms had no effect on cell viability and proliferation. Cellular expression of the fibrotic proteins galectin-3 and alpha-smooth muscle actin was not regulated by any chemerin isoform. HuChem-156 increased IL-6, IL-8 and galectin-3 in cell media. HuChem-157 was ineffective, and accordingly, did not enhance levels of these proteins in media of primary human hepatic stellate cells when added exogenously. These analyses provide evidence that huChem-156 is the biologic active chemerin variant in hepatic stellate cells and acts as a pro-inflammatory factor. |
| Databáze: | OpenAIRE |
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