Open Access

Hydrogen sulfide inhibits PCSK9 expression through the PI3K/Akt‑SREBP‑2 signaling pathway to influence lipid metabolism in HepG2 cells

  • Authors:
    • Jun Xiao
    • Xue‑Qin Bai
    • Ling Liao
    • Min Zhou
    • Juan Peng
    • Qiong Xiang
    • Zhong Ren
    • Hong‑Yan Wen
    • Zhi‑Sheng Jiang
    • Zhi‑Han Tang
    • Mei‑Mei Wang
    • Lu‑Shan Liu
  • View Affiliations

  • Published online on: March 1, 2019     https://doi.org/10.3892/ijmm.2019.4118
  • Pages: 2055-2063
  • Copyright: © Xiao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hydrogen sulfide (H2S) is an endogenous gaseous signaling molecule that plays important roles in the cardiovascular system. In our previous studies, we demonstrated that H2S regulates lipid metabolism. In the present study, we aimed to explore the mechanisms through which H2S regulates lipid metabolism in HepG2 cells in vitro. Treatment of the HepG2 cells with H2S inhibited the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9) and increased the level of low‑density lipoprotein receptor (LDLR) in a time‑ and dose‑dependent manner. The knockdown of PCSK9 by siRNA effectively increased the levels of LDLR and 1,1'‑dioctadecyl‑3,3,3',3'‑tetramethyl‑indocarbocyanine perchlorate‑labeled LDL (DiI‑LDL) uptake in the H2S‑treated HepG2 cells. Furthermore, the phosphoinositide 3‑kinase (PI3K)/protein kinase B (Akt)‑sterol regulatory element binding proteins 2 (SREBP‑2) signaling pathway was confirmed to be involved in H2S‑regulated PCSK9 expression. Notably, the HepG2 cells were incubated with 30% serum and DiI‑LDL for 24 h, and the results revealed that H2S increased lipid uptake, but caused no increase in lipid accumulation. On the whole, the findings of this study demonstrate that H2S is involved in the regulation of lipid metabolism in HepG2 cells through the regulation of the expression of PCSK9 via the PI3K/Akt‑SREBP‑2 signaling pathway. To the very best of our knowledge, this study is the first to report that H2S can regulate the expression of PCSK9.
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May-2019
Volume 43 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Copy and paste a formatted citation
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Spandidos Publications style
Xiao J, Bai XQ, Liao L, Zhou M, Peng J, Xiang Q, Ren Z, Wen HY, Jiang ZS, Tang ZH, Tang ZH, et al: Hydrogen sulfide inhibits PCSK9 expression through the PI3K/Akt‑SREBP‑2 signaling pathway to influence lipid metabolism in HepG2 cells . Int J Mol Med 43: 2055-2063, 2019.
APA
Xiao, J., Bai, X., Liao, L., Zhou, M., Peng, J., Xiang, Q. ... Liu, L. (2019). Hydrogen sulfide inhibits PCSK9 expression through the PI3K/Akt‑SREBP‑2 signaling pathway to influence lipid metabolism in HepG2 cells . International Journal of Molecular Medicine, 43, 2055-2063. https://doi.org/10.3892/ijmm.2019.4118
MLA
Xiao, J., Bai, X., Liao, L., Zhou, M., Peng, J., Xiang, Q., Ren, Z., Wen, H., Jiang, Z., Tang, Z., Wang, M., Liu, L."Hydrogen sulfide inhibits PCSK9 expression through the PI3K/Akt‑SREBP‑2 signaling pathway to influence lipid metabolism in HepG2 cells ". International Journal of Molecular Medicine 43.5 (2019): 2055-2063.
Chicago
Xiao, J., Bai, X., Liao, L., Zhou, M., Peng, J., Xiang, Q., Ren, Z., Wen, H., Jiang, Z., Tang, Z., Wang, M., Liu, L."Hydrogen sulfide inhibits PCSK9 expression through the PI3K/Akt‑SREBP‑2 signaling pathway to influence lipid metabolism in HepG2 cells ". International Journal of Molecular Medicine 43, no. 5 (2019): 2055-2063. https://doi.org/10.3892/ijmm.2019.4118