TY  - JOUR
A1  - Bittner, Stefan
A1  - Bobak, Nicole
A1  - Hofmann, Majella-Sophie
A1  - Schuhmann, Michael K.
A1  - Ruck, Tobias
A1  - Göbel, Kerstin
A1  - Brück, Wolfgang
A1  - Wiendl, Heinz
A1  - Meuth, Sven G.
T1  - Murine K\(_{2P}\)5.1 Deficiency Has No Impact on Autoimmune Neuroinflammation due to Compensatory K\(_{2P}\)3.1-and K\(_{V}\)1.3-Dependent Mechanisms
JF  - International Journal of Molecular Sciences
N2  - Lymphocytes express potassium channels that regulate physiological cell functions, such as activation, proliferation and migration. Expression levels of K\(_{2P}\)5.1(TASK2; KCNK5) channels belonging to the family of two-pore domain potassium channels have previously been correlated to the activity of autoreactive T lymphocytes in patients with multiple sclerosis and rheumatoid arthritis. In humans, K\(_{2P}\)5.1 channels are upregulated upon T cell stimulation and influence T cell effector functions. However, a further clinical translation of targeting K\(_{2P}\)5.1 is currently hampered by a lack of highly selective inhibitors, making it necessary to evaluate the impact of KCNK5 in established preclinical animal disease models. We here demonstrate that K\(_{2P}\)5.1 knockout (K\(_{2P}\)5.1\(^{-/-}\) mice display no significant alterations concerning T cell cytokine production, proliferation rates, surface marker molecules or signaling pathways. In an experimental model of autoimmune neuroinflammation, K\(_{2P}\)5.1\(^{-/-}\) mice show a comparable disease course to wild-type animals and no major changes in the peripheral immune system or CNS compartment. A compensatory upregulation of the potassium channels K\(_{2P}\)3.1 and K\(_{V}\)1.3 seems to counterbalance the deletion of K\(_{2P}\)5.1. As an alternative model mimicking autoimmune neuroinflammation, experimental autoimmune encephalomyelitis in the common marmoset has been proposed, especially for testing the efficacy of new potential drugs. Initial experiments show that K\(_{2P}\)5.1 is functionally expressed on marmoset T lymphocytes, opening up the possibility for assessing future K\(_{2P}\)5.1-targeting drugs.
KW  - domain potassium channels
KW  - volume regulation
KW  - multiple-sclerosis
KW  - potassium channels
KW  - multiple sclerosis
KW  - ion channels
KW  - K+ channel
KW  - T lymphocytes
KW  - up-regulation
KW  - TASK2
KW  - K2P channels
KW  - B cells
KW  - ph
KW  - K\(_{2P}\)5.1
KW  - KCNK5
KW  - autoimmune neuroinflammation
KW  - EAE
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151454
VL  - 16
SP  - 16880
EP  - 16896
ER  - 
TY  - JOUR
A1  - De Giorgi, Valeria
A1  - Buonaguro, Luigi
A1  - Worschech, Andrea
A1  - Tornesello, Maria Lina
A1  - Izzo, Francesco
A1  - Marincola, Francesco M.
A1  - Wang, Ena
A1  - Buonaguro, Franco M.
T1  - Molecular Signatures Associated with HCV-Induced Hepatocellular Carcinoma and Liver Metastasis
JF  - PLoS ONE
N2  - Hepatocellular carcinomas (HCCs) are a heterogeneous group of tumors that differ in risk factors and genetic alterations. In Italy, particularly Southern Italy, chronic hepatitis C virus (HCV) infection represents the main cause of HCC. Using high-density oligoarrays, we identified consistent differences in gene-expression between HCC and normal liver tissue. Expression patterns in HCC were also readily distinguishable from those associated with liver metastases. To characterize molecular events relevant to hepatocarcinogenesis and identify biomarkers for early HCC detection, gene expression profiling of 71 liver biopsies from HCV-related primary HCC and corresponding HCV-positive non-HCC hepatic tissue, as well as gastrointestinal liver metastases paired with the apparently normal peri-tumoral liver tissue, were compared to 6 liver biopsies from healthy individuals. Characteristic gene signatures were identified when normal tissue was compared with HCV-related primary HCC, corresponding HCV-positive non-HCC as well as gastrointestinal liver metastases. Pathway analysis classified the cellular and biological functions of the genes differentially expressed as related to regulation of gene expression and post-translational modification in HCV-related primary HCC; cellular Growth and Proliferation, and Cell-To-Cell Signaling and Interaction in HCV-related non HCC samples; Cellular Growth and Proliferation and Cell Cycle in metastasis. Also characteristic gene signatures were identified of HCV-HCC progression for early HCC diagnosis. 
Conclusions: A diagnostic molecular signature complementing conventional pathologic assessment was identified.
KW  - identification
KW  - hepatitis C virus
KW  - United States
KW  - gene expression
KW  - class I
KW  - endoplasmic reticulum
KW  - motile phenotype
KW  - bladder cancer
KW  - up-regulation
KW  - target
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131155
VL  - 8
IS  - 2
ER  -