Angiotensin II stimulates platelet-derived growth factor-B gene expression in cultured retinal pericytes through intracellular reactive oxygen species generation.
Platelet-derived growth factor-BB (PDGF-BB) is a potent mitogen and chemoattractant for microvascular endothelial cells and glial cells in the retina and is thus involved in the development of proliferative diabetic retinopathy. However, relatively little is known about the regulation of PDGF-B gene expression in retinal cells. In this study, we cloned partial complementary DNAs (cDNAs) encoding bovine PDGF-B and examined the effects of angiotensin II (Ang II), which is also implicated in the pathogenesis of diabetic retinopathy, on PDGF-B gene expression in bovine cultured retinal pericytes. Ang II was found to up-regulate PDGF-B messenger RNA (mRNA) levels in bovine retinal pericytes. Telmisartan, a newly developed Ang II type 1 receptor antagonist, or an antioxidant N-acetylcysteine significantly inhibited PDGF-B gene induction in Ang II-exposed pericytes. The present results suggest that Ang II-type 1 receptor interaction could stimulate PDGF-B gene expression in cultured retinal pericytes through intracellular reactive oxygen species generation and could thus be involved in the progression of diabetic retinopathy.
D000111:Acetylcysteine / Q000494:pharmacology; D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D001562:Benzimidazoles / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D003001:Cloning, Molecular; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D020286:Pericytes / Q000187:drug effects* / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep; D000077333:Telmisartan; D015533:Transcriptional Activation
D001562:Benzimidazoles; D001565:Benzoates; D020574:Proto-Oncogene Proteins c-sis; D017382:Reactive Oxygen Species; D000804:Angiotensin II; D000077333:Telmisartan; D000111:Acetylcysteine