Irbesartan inhibits albumin-elicited proximal tubular cell apoptosis and injury in vitro.
There is accumulating evidence that proteinuria is not merely a biomarker for the progression of chronic kidney disease (CKD), but also a mediator of this devastating disorder. Indeed, albumin, one of the major components found in proteinuria, causes proinflammatory and profibrotic changes in cultured proximal tubular cells. Further, numerous studies have demonstrated the active participation of the renin-angiotensin system (RAS) in the pathogenesis of CKD as well. However, the role of the RAS in albumin-elicited tubular cell damage remains to be elucidated. Therefore, in this study, we studied whether and how irbesartan, an angiotensin II type 1 receptor blocker, could inhibit albumin-elicited proximal tubular cell apoptosis and injury in vitro. Bovine serum albumin (BSA) increased oxidative stress generation in human cultured proximal tubular cells, which was blocked by the treatment with irbesartan. Irbesartan was also found to block the BSA-induced apoptotic cell death as well as up-regulation of plasminogen activator inhibitor-1 and transforming growth factor-beta mRNA levels in tubular cells. The present study suggests that there could exist a pathophysiological crosstalk between the RAS and albumin overload in proximal tubular cell apoptosis and damage. Blockade of the RAS by irbesartan may play a protective role against tubular cell injury by attenuating the deleterious effects of albumin.
Matsui
Takanori
T
Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan.
Yamagishi
Sho-ichi
S
Ueda
Seiji
S
Fukami
Kei
K
Okuda
Seiya
S
D000418:Albumins / Q000494:pharmacology; D000704:Analysis of Variance; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D000077405:Irbesartan; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012084:Renin-Angiotensin System; D013777:Tetrazoles / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
D000418:Albumins; D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C051321:SERPINE1 protein, human; D013777:Tetrazoles; D016212:Transforming Growth Factor beta; D000077405:Irbesartan