Induction of C1q expression in glomerular endothelium in a rat model with arterial hypertension and albuminuria
| Autor: | Angela Schulz, Monika Stoll, Reinhold Kreutz, Anika Sietmann, Mohamed R. Daha, Markus Wehland, Emile de Heer |
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| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty Endothelium Physiology Kidney Glomerulus Population urologic and male genital diseases Polymerase Chain Reaction Transcriptome Downregulation and upregulation Rats Inbred SHR Internal medicine Internal Medicine medicine Albuminuria Animals Rats Wistar Endothelial dysfunction education Oligonucleotide Array Sequence Analysis education.field_of_study business.industry Microarray analysis techniques Complement C1q Gene Expression Profiling CD24 Antigen medicine.disease Rats Gene expression profiling Disease Models Animal medicine.anatomical_structure Endocrinology Gene Expression Regulation Hypertension medicine.symptom Cardiology and Cardiovascular Medicine business |
| Zdroj: | Journal of Hypertension. 25:2308-2316 |
| ISSN: | 0263-6352 |
| Popis: | 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 Fromter (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. |
| Databáze: | OpenAIRE |
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