Induction of C1q expression in glomerular endothelium in a rat model with arterial hypertension and albuminuria.
OBJECTIVE
Increased urinary albumin excretion (UAE) represents an independent cardiovascular risk factor in the general population and particularly in patients with diabetes or arterial hypertension. It has been suggested that increased UAE may be related to a generalized endothelial dysfunction. We set out to identify candidate genes for increased UAE by glomerular transcriptome analysis in the Munich Wistar Frömter (MWF) genetic rat model with spontaneous hypertension and albuminuria.


METHODS
First, we performed microarray expression analysis in isolated glomerular tissue in MWF with established albuminuria and normal Wistar rats. Second, in validation experiments and follow-up studies we focused on the identified upregulation of glomerular complement component C1q expression in MWF.


RESULTS
Overall, 38 genes with a regulation score > 2 were differentially expressed in glomerular RNA. Quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR), in-situ hybridization and immunohistochemistry analysis revealed that C1q is indeed significantly upregulated in the glomerulus of MWF. Additionally, CD24, although not detected by the microarray experiment, was found to be differentially expressed in MWF glomeruli using quantitative real-time RT-PCR and immunohistochemstry. Interestingly, we could show for the first time that the glomerular endothelium represents the site of increased C1q and CD24 expression in MWF. In contrast, endothelial expression of this gene is low or absent in normotensive Wistar and in spontaneously hypertensive rats (SHR) without albuminuria.


CONCLUSIONS
The induction of C1q and CD24 expression confined to the glomerular endothelium might represent a possible repair mechanism of the capillary wall damage.
Kreutz
Reinhold
R
Institute of Clinical Pharmacology, Charité-Universitätsmedizin Berlin, Germany. reinhold.kreutz@charite.de
Schulz
Angela
A
Sietmann
Anika
A
Stoll
Monika
M
Daha
Mohamed R
MR
de Heer
Emile
E
Wehland
Markus
M
D000419:Albuminuria / Q000378:metabolism*; D000818:Animals; D051927:CD24 Antigen / Q000235:genetics / Q000502:physiology; D015922:Complement C1q / Q000235:genetics* / Q000502:physiology; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006973:Hypertension / Q000209:etiology / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar
D051927:CD24 Antigen; D015922:Complement C1q