Indoxyl Sulfate-Induced Activation of (Pro)Renin Receptor Is Involved in Expression of TGF-β1 and α-Smooth Muscle Actin in Proximal Tubular Cells
2014
Activation of (pro)renin receptor (PRR) is involved in the progression of chronic kidney disease. However, the role of
indoxyl
sulfate, a uremic toxin, in the activation of PRR is not clear. The present study aimed to clarify the role of
indoxyl
sulfatein activation of PRR, in relation to renal expression of fibrotic genes. Renal expression of PRR and renin/prorenin was up-regulated in chronic kidney disease rats compared with normal rats, whereas AST-120 suppressed these expression by reducing serum levels of
indoxyl
sulfate. Furthermore, administration of
indoxyl
sulfateto normotensive and hypertensive rats increased renal expression of PRR and renin/prorenin.
Indoxyl
sulfateinduced expression of PRR and prorenin in cultured human proximal tubular cells (HK-2 cells).
Indoxyl
sulfate-induced PRR expression was inhibited by
small interfering RNAsof signal transducer and activator of transcription 3 (Stat3) and nuclear factor-κB p65 in proximal tubular cells. N-
acetylcysteine, an antioxidant, and diphe...
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