TY  - JOUR
A1  - Preising, Christina
A1  - Schneider, Reinhard
A1  - Bucher, Michael
A1  - Gekle, Michael
A1  - Sauvant, Christoph
T1  - Regulation of expression of renal organic anion transporters OAT1 and OAT3 in a model of ischemia/reperfusion injury
JF  - Cellular Physiology and Biochemistry
N2  - Background: 
Recently, we gained evidence that impairment of rOat1 and rOat3 expression induced by ischemic acute kidney injury (AKI) is mediated by COX metabolites and this suppression might be critically involved in renal damage.
 
Methods: 
(i) Basolateral organic anion uptake into proximal tubular cells after model ischemia and reperfusion (I/R) was investigated by fluorescein uptake. The putative promoter sequences from hOAT1 (SLC22A6) and hOAT3 (SCL22A8) were cloned into a reporter plasmid, transfected into HEK cells and (ii) transcriptional activity was determined after model ischemia and reperfusion as a SEAP reporter gen assay. Inhibitors or antagonists were applied with the beginning of reperfusion. 

Results: 
By using inhibitors of PKA (H89) and PLC (U73122), antagonists of E prostanoid receptor type 2 (AH6809) and type 4 (L161,982), we gained evidence that I/R induced down regulation of organic anion transport is mediated by COX1 metabolites via E prostanoid receptor type 4. The latter signaling was confirmed by application of butaprost (EP2 agonist) or TCS2510 (EP4 agonist) to control cells. In brief, the latter signaling was verified for the transcriptional activity in the reporter gen assay established. Therein, selective inhibitors for COX1 (SC58125) and COX2 (SC560) were also applied. 

Conclusion: 
Our data show (a) that COX1 metabolites are involved in the regulation of renal organic anion transport(ers) after I/R via the EP4 receptor and (b) that this is due to transcriptional regulation of the respective transporters. As the promoter sequences cloned were of human origin and expressed in a human renal epithelial cell line we (c) hypothesize that the regulatory mechanisms described after I/R is meaningful for humans as well.
KW  - opossum kidney cells
KW  - prostaglandin e2
KW  - reperfusion
KW  - transport experiments
KW  - translation
KW  - reporter gen assay
KW  - cloning of putative human promoter sequence
KW  - regulation of expression
KW  - OAT1
KW  - OAT3
KW  - OK cells
KW  - ischemic acute kidney injury model
KW  - HEK cells
KW  - ischemia
KW  - down regulation
KW  - nitric oxide
KW  - cellular physiology
KW  - cortical OAT1
KW  - blood flow
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-144504
VL  - 37
IS  - 1
ER  - 
TY  - JOUR
A1  - Riedl, Katharina A.
A1  - Kampf, Thomas
A1  - Herold, Volker
A1  - Behr, Volker C.
A1  - Bauer, Wolfgang R.
T1  - Wall shear stress analysis using 17.6 Tesla MRI: A longitudinal study in ApoE\(^{-/-}\)mice with histological analysis
JF  - PLoS One
N2  - This longitudinal study was performed to evaluate the feasibility of detecting the interaction between wall shear stress (WSS) and plaque development. 20 ApoE\(^{-/-}\)mice were separated in 12 mice with Western Diet and 8 mice with Chow Diet. Magnetic resonance (MR) scans at 17.6 Tesla and histological analysis were performed after one week, eight and twelve weeks. Allin vivoMR measurements were acquired using a flow sensitive phase contrast method for determining vectorial flow. Histological sections were stained with Hematoxylin and Eosin, Elastica van Gieson and CD68 staining. Data analysis was performed using Ensight and a Matlab-based "Flow Tool". The body weight of ApoE\(^{-/-}\)mice increased significantly over 12 weeks. WSS values increased in the Western Diet group over the time period; in contrast, in the Chow Diet group the values decreased from the first to the second measurement point. Western Diet mice showed small plaque formations with elastin fragmentations after 8 weeks and big plaque formations after 12 weeks; Chow Diet mice showed a few elastin fragmentations after 8 weeks and small plaque formations after 12 weeks. Favored by high-fat diet, plaque formation results in higher values of WSS. With wall shear stress being a known predictor for atherosclerotic plaque development, ultra highfield MRI can serve as a tool for studying the causes and beginnings of atherosclerosis.
KW  - phase-contrast MRI
KW  - flow patterns
KW  - blood flow
KW  - apolipoprotein-E
KW  - atheriosclerosis
KW  - mouse
KW  - mice
KW  - quantification
KW  - association
KW  - lesions
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229318
VL  - 15
IS  - 8
ER  -