Medical College of Wisconsin
CTSIResearch InformaticsREDCap

Heterozygous knockout of transforming growth factor-β1 protects Dahl S rats against high salt-induced renal injury. Physiol Genomics 2013 Feb 04;45(3):110-8

Date

12/20/2012

Pubmed ID

23249995

Pubmed Central ID

PMC3568879

DOI

10.1152/physiolgenomics.00119.2012

Scopus ID

2-s2.0-84873418766 (requires institutional sign-in at Scopus site)   19 Citations

Abstract

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.

Author List

Chen CC, Geurts AM, Jacob HJ, Fan F, Roman RJ

Author

Aron Geurts PhD Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Base Sequence
Fibrosis
Gene Expression Regulation
Gene Knockout Techniques
Hypertension
Intracellular Signaling Peptides and Proteins
Kidney
Kidney Diseases
Membrane Proteins
Molecular Sequence Data
Proteinuria
Rats
Rats, Inbred Dahl
Transforming Growth Factor beta1
Transforming Growth Factor beta2
Transforming Growth Factor beta3