Original investigationsPathogenesis and treatment of kidney disease and hypertensionIncreased expression of urotensin II and urotensin II receptor in human diabetic nephropathy
Section snippets
In vivo studies
Assessment of gene expression and light microscopic studies were performed on surplus renal biopsy tissue obtained for diagnostic purposes from 7 patients with type 2 diabetic nephropathy. Biopsy specimens were divided into 3 portions. One portion was immediately snap frozen in liquid nitrogen and stored at −80°C for subsequent RNA extraction. A second portion was fixed in neutral buffered formalin and embedded in paraffin for later immunohistochemical analysis, and the third portion was frozen
Clinical data
The 7 biopsy specimens obtained for analysis were from patients with type 2 diabetes, and all had evidence of overt nephropathy, as listed in Table 1. Routine clinical biopsy evaluation did not show histopathologic changes apart from those attributable to diabetes. All patients were receiving treatment for hypertension (4 patients, angiotensin-converting enzyme inhibitors; 2 patients, calcium antagonists; 1 patient, diuretic alone). Blood pressures measured at the time of biopsy are listed in
Discussion
The present study shows dramatic overexpression of UII and its receptor in patients with diabetic nephropathy, with a 45-fold increase in ligand gene expression and an almost 2,000-fold increase in receptor expression. In addition, immunohistochemical studies localized both UII peptide and UT receptor binding to tubular epithelial cells in biopsy specimens from patients with diabetic nephropathy, whereas neither was detectable in control tissues.
To date, most studies examining UII and UT have
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2018, Biomedicine and PharmacotherapyCitation Excerpt :U-II receptor (UTR), a member of the G protein-coupled receptors (GPCRs) family also named as GPR14, is highly expressed in the cardiovascular system. In human, the expression of U-II and UTR is upregulated in cardiovascular diseases, including heart failure, hypertension, and coronary artery disease [7] as well as type 2 diabetes [8,9]. There is a positive correlation between the extent of congenital heart failure (CHF) and plasma U-II concentrations [10,11] with 2.1-fold enhancement compared with controls [12].
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Supported in part by grants from the National Health and Medical Research Council of Australia, Juvenile Diabetes Research Foundation International, and St Vincent’s Health, Melbourne. R.E.G. is a recipient of a career development award and D.J.K. is a recipient of a postdoctoral fellowship, both from Juvenile Diabetes Research Foundation International.