Prorenin independently causes hypertension and renal and cardiac fibrosis in cyp1a1-prorenin transgenic rats

Clinical Science
Guangyu ZhouYufeng Huang

Abstract

Plasma prorenin is commonly elevated in diabetic patients and appears to predict the development of diabetic nephropathy. However, the pathological role of prorenin is unclear. In the present study, a transgenic, inducible, hepatic prorenin-overexpressing rat model was generated and the effect of prorenin in organ injury was examined. Four groups of rats (cyp1a1 prorenin transgenic male and female rats and non-transgenic littermates) were assigned to receive a diet containing 0.3% of the transgene inducer indole-3-carbinol (I3C) for 4 weeks. Plasma prorenin concentration was increased and mean arterial pressure (MAP) increased from 80 ± 18 to 138 ± 17 (mmHg), whereas renal prorenin/renin protein expression was unchanged, in transgenic rats fed with I3C diet. The intact prorenin, not renin, in plasma and urine samples was further observed by Western blot analysis. Importantly, transgenic rats with high levels of prorenin developed albuminuria, glomerular and tubulointerstitial fibrosis associated with increased expression of transforming growth factor β (TGFβ) 1 (TGFβ1), plasminogen activator inhibitor-1 (PAI-1), collagen, and fibronectin (FN). These rats also exhibited cardiac hypertrophy determined by echocardiography, with el...Continue Reading

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Citations

May 19, 2020·Matrix Biology : Journal of the International Society for Matrix Biology·Mohammad AlQudahMichael P Czubryt
May 21, 2021·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Maomao HuBo Dong
Sep 1, 2021·Clinical Science·Zhimin HuangYufeng Huang

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Methods Mentioned

BETA
transgenic
PCR
dissection
ELISA
protein assay
peptide affinity chromatography
MDA

Software Mentioned

ImageJ

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