Renal endothelin-1 and endothelin receptor type B expression in glomerulardiseases with proteinuria

The endothelin (ET) system has been studied extensively in experimental mod els of progressive chronic renal disease, but there is limited information regarding the ET system in renal patients. First, the expression of human E T-1, as well as ET receptor type A (ET-R-A) and ET-R-B, was studied in 26 r enal biopsies from patients with different renal diseases. Gene expression was assessed by quantitative reverse transcription-PCR. Second, ET-1 and ET -R-B protein expression and localization were examined, by immunohistochemi cal analyses, among a homogeneous cohort of 16 patients with IgA nephropath y and different degrees of proteinuria. ET-R-B mRNA expression was threefol d higher among patients with higher-grade proteinuria [greater than or equa l to2 g/24 h, n = 10; OD ratio (ODR), i.e., wild-type/mutant mRNA ratio, 1. 81 +/- 0.3], compared with patients with lower-grade proteinuria (<2 g/24 h , n = 8; ODR, 0.63 <plus/minus> 0.1; P < 0.01) or control subjects (n = 9; ODR, 0.57 <plus/minus> 0.1; P < 0.01). ET-1 gene expression was significant ly higher among patients with higher-grade proteinuria, compared with patie nts with lower-grade proteinuria (P < 0.01) or control subjects (P < 0.05). ET-R-A mRNA expression was not different among the groups. Patients with h igher-grade proteinuria who were receiving angiotensin-converting enzyme in hibitors exhibited significantly (P < 0.05) lower ET-1 and ET-R-B mRNA expr ession, which was comparable to that of control subjects. By using immunohi stochemical analyses, an association between proteinuria and expression of ET-1 and ET-R-B in proximal tubular epithelial cells and of ET-1 in glomeru li was confirmed in the separate cohort of patients with IgA nephropathy. I t is concluded that the increased ET-R-B and ET-1 mRNA and protein expressi on observed in animal models of renal disease is also demonstrable among pa tients with renal disease and high-grade proteinuria.