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Chemerin Isoform-Specific Effects on Hepatocyte Migration and Immune Cell Inflammation
Article

Chemerin-156 is the Active Isoform in Human Hepatic Stellate Cells

1
Department of Internal Medicine I, Regensburg University Hospital, 93053 Regensburg, Germany
2
Department of Pharmacology, Dalhousie University, Halifax, NS B3H 4R2, Canada
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(20), 7555; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21207555
Received: 23 September 2020 / Revised: 8 October 2020 / Accepted: 12 October 2020 / Published: 13 October 2020
(This article belongs to the Special Issue Adipokines 3.0)
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. View Full-Text
Keywords: Galectin-3; IL-6; Proliferation; Tango Assay; CMKLR1 Galectin-3; IL-6; Proliferation; Tango Assay; CMKLR1
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MDPI and ACS Style

Spirk, M.; Zimny, S.; Neumann, M.; McMullen, N.; Sinal, C.J.; Buechler, C. Chemerin-156 is the Active Isoform in Human Hepatic Stellate Cells. Int. J. Mol. Sci. 2020, 21, 7555. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21207555

AMA Style

Spirk M, Zimny S, Neumann M, McMullen N, Sinal CJ, Buechler C. Chemerin-156 is the Active Isoform in Human Hepatic Stellate Cells. International Journal of Molecular Sciences. 2020; 21(20):7555. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21207555

Chicago/Turabian Style

Spirk, Marlen, Sebastian Zimny, Maximilian Neumann, Nichole McMullen, Christopher J. Sinal, and Christa Buechler. 2020. "Chemerin-156 is the Active Isoform in Human Hepatic Stellate Cells" International Journal of Molecular Sciences 21, no. 20: 7555. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21207555

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