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Plasminogen activator inhibitor-1 deficiency protects against aldosterone-induced glomerular injury
- Source :
- Kidney International. (6):1064-1072
- Publisher :
- International Society of Nephrology. Published by Elsevier Inc.
-
Abstract
- This study tests the hypothesis that plasminogen activator inhibitor-1 (PAI-1) contributes to aldosterone-induced renal and cardiac injury. The effects of 12-week aldosterone (2.8 microg/day)/salt (1% drinking water) versus vehicle/salt on renal and cardiac histology and mRNA expression were determined in wild-type (WT) and PAI-1 deficient (PAI-1(-/-)) mice. Systolic blood pressure was similar in aldosterone-infused WT and PAI-1(-/-) mice until 12 weeks, when it was significantly higher in the WT mice. At 12 weeks, urine volume, sodium excretion, and sodium/potassium ratio were similarly increased in the two aldosterone-infused groups. In contrast, urine albumin excretion was greater in aldosterone-infused WT mice (mean+/-s.d.: 699.0+/-873.0 microg/24 h) compared to vehicle-infused WT (23.6+/-9.0 microg/24 h, P=0.003) or aldosterone-infused PAI-1(-/-) mice (131.6+/-110.6 microg/24 h, P=0.007). Aldosterone increased glomerular area to a greater extent in WT (4651+/-577 versus 3278+/-488 microm2/glomerulus in vehicle-infused WT, P0.001) than in PAI-1(-/-) mice (3713+/-705 microm2/glomerulus, P=0.001 versus aldosterone-infused WT), with corresponding mesangial expansion. Renal collagen content was also increased in aldosterone-infused WT versus PAI-1(-/-) mice. In WT mice, aldosterone increased renal mRNA expression of PAI-1, collagen I, collagen III, osteopontin, fibronectin, monocyte chemoattractant protein-1 (MCP-1), and F4/80 (all P0.05), but not transforming growth factor beta (TGF-beta). In PAI-1(-/-) mice, aldosterone increased renal expression of collagen I, osteopontin, fibronectin, and MCP-1, and tended to increase collagen III. Renal osteopontin expression was diminished in aldosterone-treated PAI-1(-/-) compared to aldosterone-treated WT mice (P=0.05). Aldosterone induced cardiac hypertrophy but not fibrosis in WT and PAI-1(-/-) mice. PAI-1 contributes to aldosterone-induced glomerular injury.
- Subjects :
- Male
medicine.medical_specialty
medicine.drug_class
Sialoglycoproteins
Sodium
Kidney Glomerulus
Gene Expression
chemistry.chemical_element
Blood Pressure
Mice, Inbred Strains
Nephrectomy
Mice
chemistry.chemical_compound
Glomerulonephritis
Internal medicine
Plasminogen Activator Inhibitor 1
Renin–angiotensin system
medicine
Albuminuria
Animals
RNA, Messenger
Osteopontin
Chemokine CCL2
Aldosterone
aldosterone
biology
Macrophages
Myocardium
Hemodynamics
angiotensin
medicine.disease
Fibronectins
Mice, Inbred C57BL
Endocrinology
chemistry
Nephrology
Mineralocorticoid
Plasminogen activator inhibitor-1
biology.protein
plasminogen activator inhibitor-1
Collagen
Plasminogen activator
Subjects
Details
- Language :
- English
- ISSN :
- 00852538
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Kidney International
- Accession number :
- edsair.doi.dedup.....2ba57a478f6540f9577717388f64e23d
- Full Text :
- https://doi.org/10.1038/sj.ki.5000201