Next Article in Journal
A Mixture of Persistent Organic Pollutants and Perfluorooctanesulfonic Acid Induces Similar Behavioural Responses, but Different Gene Expression Profiles in Zebrafish Larvae
Next Article in Special Issue
Action of Thyroid Hormones, T3 and T2, on Hepatic Fatty Acids: Differences in Metabolic Effects and Molecular Mechanisms
Previous Article in Journal
High-Level γ-Glutamyl-Hydrolase (GGH) Expression is Linked to Poor Prognosis in ERG Negative Prostate Cancer
Previous Article in Special Issue
Identification of Proteins Interacting with Cytoplasmic High-Mobility Group Box 1 during the Hepatocellular Response to Ischemia Reperfusion Injury
Open AccessArticle

Decreased Expression of Vitamin D Receptor Affects an Immune Response in Primary Biliary Cholangitis via the VDR-miRNA155-SOCS1 Pathway

1
Department of Medical Biology, Pomeranian Medical University, 70-111 Szczecin, Poland
2
Department of General Transplant and Liver Surgery, Medical University of Warsaw, 02-097 Warszawa, Poland
3
Translation Medicine Group, Pomeranian Medical University, 70-111 Szczecin, Poland
4
Liver and Internal Medicine Unit, Medical University of Warsaw, 02-097 Warszawa, Poland
*
Author to whom correspondence should be addressed.
Academic Editor: Johannes Haybaeck
Int. J. Mol. Sci. 2017, 18(2), 289; https://doi.org/10.3390/ijms18020289
Received: 18 December 2016 / Revised: 23 January 2017 / Accepted: 25 January 2017 / Published: 29 January 2017
(This article belongs to the Collection Molecular Mechanisms of Human Liver Diseases)
Primary biliary cholangitis (PBC) is an immune-mediated cholestatic disease. Vitamin D receptor (VDR)-dependent signaling constrains an inflammatory response by targeting the miRNA155-SOCS1 (suppressor of cytokine signaling 1) axis. The VDR-miRNA155-SOCS1 pathway was investigated in the context of the autoimmune response associated with PBC. Human liver tissues from non-cirrhotic PBC (n = 22), cirrhotic PBC (n = 22), cirrhotic primary sclerosing cholangitis (PSC, n=13), controls (n = 23), and peripheral blood mononuclear cells (PBMC) obtained from PBC (n = 16) and PSC (n = 10) patients and healthy subjects (n = 11) were used for molecular analyses. VDR mRNA and protein expressions were substantially reduced in PBC livers (51% and 59%, respectively). Correspondingly, the decrease of SOCS1 protein expression in PBC livers, after normalization to a marker of lymphocytes and forkhead family transcriptional regulator box P3 (FOXP3, marker of Treg), was observed, and this phenomenon was accompanied by enhanced miRNA155 expression. In PSC livers, protein expressions of VDR and SOCS1 were comparable to the controls. However, in PBM cells, protein expressions of VDR and SOCS1 were considerably decreased in both PBC and PSC. We demonstrated that VDR/miRNA155-modulated SOCS1 expression is decreased in PBC which may lead to insufficient negative regulation of cytokine signaling. These findings suggest that the decreased VDR signaling in PBC could be of importance in the pathogenesis of PBC. View Full-Text
Keywords: vitamin D receptor; suppressor of cytokine signaling 1 (SOCS1); miR-155; cholestatic liver disease vitamin D receptor; suppressor of cytokine signaling 1 (SOCS1); miR-155; cholestatic liver disease
Show Figures

Figure 1

MDPI and ACS Style

Kempinska-Podhorodecka, A.; Milkiewicz, M.; Wasik, U.; Ligocka, J.; Zawadzki, M.; Krawczyk, M.; Milkiewicz, P. Decreased Expression of Vitamin D Receptor Affects an Immune Response in Primary Biliary Cholangitis via the VDR-miRNA155-SOCS1 Pathway. Int. J. Mol. Sci. 2017, 18, 289.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop