Activation of the Nrf2-ARE Signaling Pathway Prevents Hyperphosphatemia-Induced Vascular Calcification by Inducing Autophagy in Renal Vascular Smooth Muscle Cells.
J Cell Biochem
; 118(12): 4708-4715, 2017 12.
Article
em En
| MEDLINE
| ID: mdl-28513870
ABSTRACT
This study investigates the effect of nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) signaling pathway in vascular calcification (VC) via inducing Autophagy in renal vascular smooth muscle cells (VSMCs). VSMCs were assigned into six experimental groups the normal control, high phosphorus, si-negative control (si-NC), Nrf2-siRNA, over-expressed Nrf2, and negative control (NC) groups. RT-PCR was applied to detect the mRNA expressions of the desired Nrf2-ARE signaling pathway-related genes (Nrf2, NQO-1, HO-1, γ-GCS). The protein products of these genes apoptosis-related genes (LC3I and LC3II), osteogenic marker proetins (Runt-related transcription factor 2) Runx2 and BMP2 were all detected by Western blotting. Autophagosomes in VSMCs were observed under a transmission electron microscope. We discovered an increased calcium ion concentration and upregulated Runx2, BMP2, Nrf2, HO-1, γ-GCS, NQO-1, and LC3II/LC3I expressions in the high phosphorous, si-NC and Nrf2-siRNA, and NC groups, compared with the normal control group. Compared to the high phosphorus and si-NC groups, higher levels of Runx2 and BMP2 but decreased Nrf2, HO-1, γ-GCS, NQO-1, and LC3II/LC3I expressions were detected in the Nrf2-siRNA group. The high phosphorus, si-NC and over-expressed Nrf2 experimental groups all had increased Nrf2, NQO-1, HO-1, γ-GCS, and LC3II/LC3I expressions as well as high numbers of autophagosomes compared with the normal control group. Finally, we detected a lower amount of autophagosomes presence and Nrf2, NQO-1, HO-1 γ-GCS, and LC3II/LC3 protein expression of Nrf2-siRNA group than that of the high phosphorus and si-NC groups. Activation of Nrf2-ARE signaling pathway may prevent hyperphosphatemia-induced VC by inducing autophagy in VSMCs. J. Cell. Biochem. 118 4708-4715, 2017. © 2017 Wiley Periodicals, Inc.
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MEDLINE
Assunto principal:
Autofagia
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Transdução de Sinais
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Elementos de Resposta
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Miócitos de Músculo Liso
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Fator 2 Relacionado a NF-E2
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Hiperfosfatemia
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Calcificação Vascular
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Músculo Liso Vascular
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article