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Antihypertensive therapy induces compartment-specific chemokine expression and a Th1 immune response in the clipped kidney of Goldblatt hypertensive rats
- Source :
- American journal of physiology-Renal physiology, 292(2), F876-F887. AMER PHYSIOLOGICAL SOC
- Publication Year :
- 2007
- Publisher :
- AMER PHYSIOLOGICAL SOC, 2007.
-
Abstract
- The present study examined the pathogenesis of interstitial inflammation and fibrosis in antihypertensively treated rats with two-kidney, one-clip hypertension. Hypertensive rats were randomized into four groups: no treatment and moderate, intermediate, and intensified lowering of blood pressure with increasing doses of a vasopeptidase inhibitor for 6 wk. 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 and the Th1-type chemokines IP10 and Mig as well as their receptor CXCR3 and the Th1 cytokine IFN-γ. 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 the appearance of myofibroblasts and synthesis of the fibrogenic factor plasminogen activator inhibitor-1 as well as the collagenase matrix metalloproteinase-2, leading to collagen I 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 therapeutic interventions in ischemic nephropathy.
- Subjects :
- Male
Chemokine
renovascular hypertension
Physiology
PAI-1
Gene Expression
chemokines
Kidney
CXCR3
Chemokine CXCL9
Renovascular hypertension
Rats, Sprague-Dawley
Pathogenesis
Fibrosis
NITRENDIPINE
Chemokine CCL2
In Situ Hybridization
biology
Mig
matrix metalloproteinases
Intercellular Adhesion Molecule-1
Immunohistochemistry
Hypertension, Renovascular
medicine.anatomical_structure
INFILTRATION
REJECTION
Th1 response
Creatinine
Matrix Metalloproteinase 2
Chemokines, CXC
Heterocyclic Compounds, 3-Ring
medicine.medical_specialty
acute renal failure
Interferon-gamma
Internal medicine
Plasminogen Activator Inhibitor 1
medicine
Renal fibrosis
INJURY
Animals
RENAL FIBROSIS
Antihypertensive Agents
business.industry
2-KIDNEY
NEPHROSCLEROSIS
Th1 Cells
medicine.disease
Actins
Rats
Chemokine CXCL10
vasopeptidase inhibition
Endocrinology
biology.protein
Osteopontin
IP10
business
Kidney disease
MCP-1
Subjects
Details
- Language :
- English
- ISSN :
- 15221466 and 1931857X
- Volume :
- 292
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- American journal of physiology-Renal physiology
- Accession number :
- edsair.doi.dedup.....c24fbaf0cf3b11a8ad8ce95c5422c34a