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

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

Department of Internal Medicine I, Regensburg University Hospital, 93053 Regensburg, Germany
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;
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.

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.

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.

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