Lack of nidogen-2 increases blood pressure, glomerular and tubulointerstitial damage in DOCA-salt hypertension
| Autor: | Kerstin Benz, C. S. Haas, Andrea Hartner, G. A. Zeiler, Kerstin Amann, Karl F. Hilgers, B. L. Bader |
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| Rok vydání: | 2009 |
| Předmět: |
Male
endocrine system medicine.medical_specialty Hypertension Renal animal structures medicine.medical_treatment Clinical Biochemistry Blood Pressure Biology Nephrectomy Biochemistry Mice chemistry.chemical_compound Laminin Mineralocorticoids Internal medicine Glomerular Basement Membrane medicine Albuminuria Animals Desoxycorticosterone Mice Knockout Kidney Creatinine Membrane Glycoproteins Mesangial cell Glomerular basement membrane Calcium-Binding Proteins Glomerulosclerosis General Medicine medicine.disease medicine.anatomical_structure Endocrinology chemistry biology.protein Nidogen-2 Cell Adhesion Molecules |
| Zdroj: | European Journal of Clinical Investigation. 39:116-125 |
| ISSN: | 1365-2362 0014-2972 |
| DOI: | 10.1111/j.1365-2362.2008.02065.x |
| Popis: | Background Nidogen-2, an extracellular matrix protein, is ubiquitous in renal basement membranes linking the laminin and collagen IV networks. Nidogen-2-deficient (nidogen-2−/–) mice do not exhibit a phenotype, and renal basement membranes appear normal. The functional role of nidogen-2 in the adult kidney under pathological conditions however remains unclear. We tested the hypothesis that nidogen-2 mediated cell-matrix interactions are important to maintain glomerular integrity and structure in renal hyperperfusion and hypertension. Materials and methods Two weeks after unilateral nephrectomy (UNX), desoxycorticosterone (DOCA)-salt hypertension was induced in nidogen-2−/– mice and their wild type littermates for 6 weeks. Renal damage was assessed by means of semiquantitative scoring, morphometric analysis, immunohistochemistry and measurement of serum creatinine and albumin excretion. Results UNX alone resulted in a very mild increase in renal damage in nidogen-2−/– mice compared to wild type animals. Following DOCA-salt treatment, blood pressure, serum creatinine and albumin excretion were significantly higher in nidogen-2−/– than in wild type mice. In addition, nidogen-2−/– mice showed increased mesangial cell hyperplasia and matrix expansion with higher expression of fibronectin and its receptor α8 integrin. Glomerular capillaries were significantly reduced in size and number. Conclusions We demonstrate that in both mild and severe glomerular damage, lack of nidogen-2 is associated with: (i) increased mesangioproliferation; (ii) higher mesangial matrix expansion; and (iii) reduction in glomerular capillary supply. These findings suggest a critical role for nidogen-2 in the maintenance of glomerular structure in the diseased kidney. |
| Databáze: | OpenAIRE |
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