Heterozygous knockout of transforming growth factor-β1 protects Dahl S rats against high salt-induced renal injury
| Autor: | Aron M. Geurts, Fan Fan, Howard J. Jacob, Chun Cheng Andy Chen, Richard J. Roman |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Physiology Molecular Sequence Data Kidney Transforming Growth Factor beta1 Gene Knockout Techniques Transforming Growth Factor beta2 Transforming Growth Factor beta3 Fibrosis Internal medicine Genetics medicine Renal fibrosis Animals Regulation of gene expression Nuclease Rats Inbred Dahl biology Base Sequence Intracellular Signaling Peptides and Proteins Membrane Proteins medicine.disease Rats Proteinuria Endocrinology medicine.anatomical_structure Gene Expression Regulation Renal physiology Hypertension biology.protein Call for Papers Kidney Diseases Transforming growth factor |
| Zdroj: | Physiological genomics. 45(3) |
| ISSN: | 1531-2267 |
| Popis: | The present study employed a zinc-finger nuclease strategy to create heterozygous knockout (KO) rats for the transforming growth factor-β1 ( Tgfb1) gene on the Dahl SS/Jr genetic background (TGF-β1+/−Dahl S). Intercrossing TGF-β1+/−rats did not produce any homozygous KO rats (66.4% +/−, 33.6% +/+), indicating that the mutation is embryonic lethal. Six-week-old wild-type (WT) littermates and TGF-β1+/−Dahl S rats were fed a 0.4% (low salt, LS) or 8% NaCl (high salt, HS) diet for 5 wk. Renal cortical expression of TGF-β1, urinary TGF-β1 excretion, proteinuria, glomerular injury and tubulointerstitial fibrosis, and systolic blood pressure were similar in WT and TGF-β1+/−Dahl S rats maintained on the LS diet. The expression and urinary excretion of TGF-β1 increased to a greater extent in WT than in TGF-β1+/−Dahl S rats fed an HS diet for 1 wk. Systolic blood pressure rose by the same extent to 235 ± 2 mmHg in WT and 239 ± 4 mmHg in TGF-β1+/−Dahl S rats fed a HS diet for 5 wk. However, urinary protein excretion was significantly lower in TGF-β1+/−Dahl S than in the WT animals. The degree of glomerular injury and renal cortical and outer medullary fibrosis was markedly less in TGF-β1+/−than in WT rats. These findings suggest that the loss of one copy of the TGF-β1 gene blunts the increase in renal TGF-β1 protein expression and slows the progression of proteinuria, glomerulosclerosis, and renal interstitial fibrosis in Dahl S rats fed an HS diet independently of changes in blood pressure. |
| Databáze: | OpenAIRE |
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