Internephron heterogeneity of growth factors and sclerosis--modulation of platelet-derived growth factor by angiotensin II

Abstract

We studied the early phase after 5/6 nephrectomy in Munich-Wistar rats to determine whether treatment with angiotensin II receptor antagonist (AIIRA) modulates the expression of platelet-derived growth factor (PDGF) mRNA and its protein among the glomeruli which are undergoing progressive hypertrophy and sclerosis. Average PDGF-B immunohistochemistry staining score (IHS, 0 to 3 scale) in glomeruli and PDGF-B chain mRNA from kidneys were both increased in 5/6 nephrectomy rats (N = 6) versus age-matched normal (N = 5) at week 4, when glomeruli were at early stages of sclerosis (IHS, 0.81 +/- 0.12 vs. 0.19 +/- 0.05; sclerosis index, S.I., 0 to 4 scale: 0.41 +/- 0.04 vs. 0.05 +/- 0.01, both P < 0.05). AIIRA (80 mg/liter drinking water, N = 6) started at time of 5/6 nephrectomy prevented the development of sclerosis (S.I. 0.08 +/- 0.03) and decreased PDGF-B protein (IHS 0.22 +/- 0.08, both P = NS vs. normal), and PDGF-B chain mRNA. In contrast, triple therapy (TRX; hydralazine, reserpine and hydrochlorothiazide, N = 5) in doses which controlled systemic blood pressure resulted in intermediate level of glomerulosclerosis at this early time point of progressive injury. Concurrently, TRX failed to affect the expression of PDGF-B protein (IHS 0.86 +/- 0.19) or its mRNA expression. The PDGF-B distribution was not uniform amongst the glomeruli with varying stages of sclerosis. There was a strong correlation in individual glomeruli of increased PDGF-B staining with early sclerotic changes (P < 0.01), with the disappearance of this correlation in glomeruli with advanced sclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)