TY  - JOUR
A1  - Rosenbaum, Corinna
A1  - Schick, Martin Alexander
A1  - Wollborn, Jakob
A1  - Heider, Andreas
A1  - Scholz, Claus-Jürgen
A1  - Cecil, Alexander
A1  - Niesler, Beate
A1  - Hirrlinger, Johannes
A1  - Walles, Heike
A1  - Metzger, Marco
T1  - Activation of Myenteric Glia during Acute Inflammation In Vitro and In Vivo
JF  - PLoS One
N2  - Background
Enteric glial cells (EGCs) are the main constituent of the enteric nervous system and share similarities with astrocytes from the central nervous system including their reactivity to an inflammatory microenvironment. Previous studies on EGC pathophysiology have specifically focused on mucosal glia activation and its contribution to mucosal inflammatory processes observed in the gut of inflammatory bowel disease (IBD) patients. In contrast knowledge is scarce on intestinal inflammation not locally restricted to the mucosa but systemically affecting the intestine and its effect on the overall EGC network.

Methods and Results
In this study, we analyzed the biological effects of a systemic LPS-induced hyperinflammatory insult on overall EGCs in a rat model in vivo, mimicking the clinical situation of systemic inflammation response syndrome (SIRS). Tissues from small and large intestine were removed 4 hours after systemic LPS-injection and analyzed on transcript and protein level. Laser capture microdissection was performed to study plexus-specific gene expression alterations. Upon systemic LPS-injection in vivo we observed a rapid and dramatic activation of Glial Fibrillary Acidic Protein (GFAP)-expressing glia on mRNA level, locally restricted to the myenteric plexus. To study the specific role of the GFAP subpopulation, we established flow cytometry-purified primary glial cell cultures from GFAP promotor-driven EGFP reporter mice. After LPS stimulation, we analyzed cytokine secretion and global gene expression profiles, which were finally implemented in a bioinformatic comparative transcriptome analysis. Enriched GFAP+ glial cells cultured as gliospheres secreted increased levels of prominent inflammatory cytokines upon LPS stimulation. Additionally, a shift in myenteric glial gene expression profile was induced that predominantly affected genes associated with immune response.

Conclusion and Significance
Our findings identify the myenteric GFAP-expressing glial subpopulation as particularly susceptible and responsive to acute systemic inflammation of the gut wall and complement knowledge on glial involvement in mucosal inflammation of the intestine.
KW  - gene expression
KW  - gastrointestinal tract
KW  - inflammatory bowel disease
KW  - central nervous system
KW  - systemic inflammatory response syndrome
KW  - inflammation
KW  - astrocytes
KW  - cytokines
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146544
VL  - 11
IS  - 3
ER  - 
TY  - JOUR
A1  - Pfeiffer, Susanne
A1  - Krüger, Jacqueline
A1  - Maierhofer, Anna
A1  - Böttcher, Yvonne
A1  - Klöting, Nora
A1  - El Hajj, Nady
A1  - Schleinitz, Dorit
A1  - Schön, Michael R.
A1  - Dietrich, Arne
A1  - Fasshauer, Mathias
A1  - Lohmann, Tobias
A1  - Dreßler, Miriam
A1  - Stumvoll, Michael
A1  - Haaf, Thomas
A1  - Blüher, Matthias
A1  - Kovacs, Peter
T1  - Hypoxia-inducible factor 3A gene expression and methylation in adipose tissue is related to adipose tissue dysfunction
JF  - Scientific Reports
N2  - Recently, a genome-wide analysis identified DNA methylation of the HIF3A (hypoxia-inducible factor 3A) as strongest correlate of BMI. Here we tested the hypothesis that HIF3A mRNA expression and CpG-sites methylation in adipose tissue (AT) and genetic variants in HIF3A are related to parameters of AT distribution and function. In paired samples of subcutaneous AT (SAT) and visceral AT (VAT) from 603 individuals, we measured HIF3A mRNA expression and analyzed its correlation with obesity and related traits. In subgroups of individuals, we investigated the effects on HIF3A genetic variants on its AT expression (N = 603) and methylation of CpG-sites (N = 87). HIF3A expression was significantly higher in SAT compared to VAT and correlated with obesity and parameters of AT dysfunction (including CRP and leucocytes count). HIF3A methylation at cg22891070 was significantly higher in VAT compared to SAT and correlated with BMI, abdominal SAT and VAT area. Rs8102595 showed a nominal significant association with AT HIF3A methylation levels as well as with obesity and fat distribution. HIF3A expression and methylation in AT are fat depot specific, related to obesity and AT dysfunction. Our data support the hypothesis that HIF pathways may play an important role in the development of AT dysfunction in obesity.
KW  - gene expression
KW  - adipose
KW  - hypoxia-inducible factor 3A
KW  - adipose tissue dysfunction
KW  - obesity
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167662
VL  - 6
IS  - 27969
ER  -