| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Medicine, University Hospital Hamburg, Hamburg, Germany
2 Clinical Chemistry, University Hospital Hamburg, Hamburg, Germany
3 Molecular Neurobiology, University Hospital Hamburg, Hamburg, Germany
4 Department of Pathology, UMCG Groningen, Groningen, Netherlands
5 Medizinische Kllnik, Universitatskrankenhays Eppendorf, Abteilung Nephrologie/Osteologie, Hamburg, 20246, Germany; Medicine, University Hospital Hamburg, Hamburg, Germany
* To whom correspondence should be addressed. E-mail: wenzel{at}uke.uni-hamburg.de.
The present study examined the pathogenesis of interstitial inflammation and fibrosis in antihypertensively treated rats with 2 kidney, 1 clip hypertension. Hypertensive rats were randomized into four groups: no treatment, moderate, intermediate and intensified lowering of blood pressure with increasing doses of a vasopeptidase inhibitor for 6 weeks. The vasopeptidase inhibitor dose dependently lowered blood pressure. The tubulointerstitial damage was accompanied by a diffuse infiltration of mononuclear cells and circumscript mononuclear inflammatory cell cluster formation consisting mainly of T cells and to a lesser degree of macrophages and B cells. Real time PCR analyses showed a dose dependent induction of MCP-1, the Th1 type chemokines IP10 and Mig as well as their receptor CXCR3 and the Th1 cytokine IFN gamma. In situ hybridization and laser microdissection revealed a strong expression of these Th1 associated transcripts in the clusters and in the case of MCP-1 also diffusely in the interstitium. The inflammation was accompanied by appearance of myofibroblasts and synthesis of the fibrogenic factor PAI-1, as well as the collagenase MMP-2 leading to collagen 1 upregulation and interstitial scarring. No inflammation or fibrosis was found in normotensive rats treated with the vasopeptidase inhibitor. The renal injury in the clipped kidney is accompanied by compartment specific chemokine expression and cell cluster formation of Th1 specificity associated with upregulation of fibrogenic proteins and matrix metalloproteinases. These findings suggest that the Th1 chemokines IP10 and Mig as well as their receptor CXCR3 are potential targets for therapeutical interventions in ischemic nephropathy.
This article has been cited by other articles:
|
|
 |
|
  H.-J. Paust, J.-E. Turner, O. M. Steinmetz, A. Peters, F. Heymann, C. Holscher, G. Wolf, C. Kurts, H.-W. Mittrucker, R. A.K. Stahl, et al. The IL-23/Th17 Axis Contributes to Renal Injury in Experimental Glomerulonephritis J. Am. Soc. Nephrol., May 1, 2009; 20(5): 969 - 979. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Meyer-Schwesinger, S. Dehde, C. von Ruffer, S. Gatzemeier, P. Klug, U. O. Wenzel, R. A. K. Stahl, F. Thaiss, and T. N. Meyer Rho kinase inhibition attenuates LPS-induced renal failure in mice in part by attenuation of NF-{kappa}B p65 signaling Am J Physiol Renal Physiol, May 1, 2009; 296(5): F1088 - F1099. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. N. Muller, B. Klanke, S. Feldt, N. Cordasic, A. Hartner, R. E. Schmieder, F. C. Luft, and K. F. Hilgers (Pro)Renin Receptor Peptide Inhibitor "Handle-Region" Peptide Does Not Affect Hypertensive Nephrosclerosis in Goldblatt Rats Hypertension, March 1, 2008; 51(3): 676 - 681. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
