Expression and localization of PDGF-B, PDGF-D, and PDGF receptor in the kidney of angiotensin II-infused rat.

Lipid accumulation in the kidney is a marker of tissue damage and may play a role in the development of renal injury. We have previously shown that long-term administration of angiotensin II in rats causes increased expression of transforming growth factor-beta1, coupled with an accumulation of lipids in the tubular and vascular wall cells in the kidney. In this study, we examine the regulation of expression of platelet-derived growth factor (PDGF) and its receptor system and their co-localization with lipid deposits in the kidneys of angiotensin II-infused rats. Real-time RT-PCR showed that expression of PDGF-B, PDGF-D, and PDGF receptor-beta (PDGFR-beta) mRNA was increased by angiotensin II infusion, and in situ hybridization showed the co-localization of these mRNAs. Tubular cells that had increased PDGF-B mRNA expression were positive for lipid deposition and also for cellular proliferation, which was indicated by the presence of proliferating cell nuclear antigen. By contrast, in the kidneys of angiotensin II-infused rats, apoptosis occurred in tubular cells that contained deposits of iron but not lipids. The deposition of lipids and upregulation of PDGF-B, PDGF-D, and PDGFR-beta induced by administration of angiotensin II were all suppressed by the selective angiotensin II type 1 (AT(1)) receptor antagonist losartan, but not by the nonspecific vasodilator hydralazine. The findings that lipid accumulation, upregulation of PDGF-B, PDGF-D, and PDGFR-beta, and cellular proliferation were topologically associated and regulated in an AT(1) receptor-dependent manner in the kidney of angiotensin II-infused rats suggests that these phenomena are related.