| First Author | Amann K | Year | 2009 |
| Journal | Eur J Clin Invest | Volume | 39 |
| Issue | 2 | Pages | 116-25 |
| PubMed ID | 19200165 | Mgi Jnum | J:164987 |
| Mgi Id | MGI:4835855 | Doi | 10.1111/j.1365-2362.2008.02065.x |
| Citation | Amann K, et al. (2009) Lack of nidogen-2 increases blood pressure, glomerular and tubulointerstitial damage in DOCA-salt hypertension. Eur J Clin Invest 39(2):116-25 |
| abstractText | 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 alpha8 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. |
