Indoxyl Sulfate-Induced Activation of Prorenin Receptor Promotes Cell Proliferation and Tissue Factor Expression in Vascular Smooth Muscle CellsReportar como inadecuado




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Chronic kidney disease CKD is associated with an increased risk of cardiovascular disease CVD. Prorenin receptor PRR is activated in the kidney of CKD. The present study aimed to determine the role of indoxyl sulfate IS, a uremic toxin, in PRR activation in rat aorta and human aortic smooth muscle cells HASMCs. We examined the expression of PRR and renin-prorenin in rat aorta using immunohistochemistry. Both CKD rats and IS-administrated rats showed elevated expression of PRR and renin-prorenin in aorta compared with normal rats. IS upregulated the expression of PRR and prorenin in HASMCs. N-acetylcysteine, an antioxidant, and diphenyleneiodonium, an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase, suppressed IS-induced expression of PRR and prorenin in HASMCs. Knock down of organic anion transporter 3 OAT3, aryl hydrocarbon receptor AhR and nuclear factor-κB p65 NF-κB p65 with small interfering RNAs inhibited IS-induced expression of PRR and prorenin in HASMCs. Knock down of PRR inhibited cell proliferation and tissue factor expression induced by not only prorenin but also IS in HASMCs.

Conclusion

IS stimulates aortic expression of PRR and renin-prorenin through OAT3-mediated uptake, production of reactive oxygen species, and activation of AhR and NF-κB p65 in vascular smooth muscle cells. IS-induced activation of PRR promotes cell proliferation and tissue factor expression in vascular smooth muscle cells.



Autor: Maimaiti Yisireyili, Shinichi Saito, Shaniya Abudureyimu, Yelixiati Adelibieke, Hwee-Yeong Ng, Fuyuhiko Nishijima, Kyosuke Takesh

Fuente: http://plos.srce.hr/



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