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内脂素受白细胞介素-6 调控,并受 BeWo 细胞中过氧化物酶体增殖物激活受体-γ 通路的影响。

Visfatin is regulated by interleukin‑6 and affected by the PPAR‑γ pathway in BeWo cells.

机构信息

Department of Obstetrics, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China.

Department of Obstetrics, Cangzhou People's Hospital, Cangzhou, Hebei 061000, P.R. China.

出版信息

Mol Med Rep. 2019 Jan;19(1):400-406. doi: 10.3892/mmr.2018.9671. Epub 2018 Nov 20.

Abstract

Visfatin, an adipocytokine and cytosolic enzyme with nicotinamide phosphoribosyltransferase (Nampt) activity, is involved in the pathogenesis of numerous metabolic disorders. In addition, the nuclear receptor peroxisome proliferator‑activated receptor‑γ (PPAR‑γ) serves important roles in anti‑inflammatory reactions and regulates glucose and lipid metabolism. The aim of the present study was to investigate the effect of interleukin‑6 (IL‑6) on the expression and secretion of visfatin in BeWo cells, and to determine whether the PPAR‑γ pathway is involved in the regulation of visfatin by IL‑6. Therefore, BeWo cells were stimulated with serial concentrations of IL‑6 or pioglitazone, and the expression levels of visfatin and PPAR‑γ were determined by reverse transcription‑quantitative polymerase chain reaction and western blotting. The results of the present study demonstrated that IL‑6 downregulated the mRNA levels of visfatin and PPAR‑γ, which were strongly associated. Activation of PPAR‑γ by pioglitazone resulted in significantly increased expression of visfatin, which abrogated the inhibitory effect of IL‑6 on visfatin in BeWo cells. Furthermore, treatment using pioglitazone alone increased the expression and secretion of the visfatin protein, compared with the control or IL‑6 alone group. In summary, the findings of the present study suggested that IL‑6 inhibited the expression of visfatin and PPAR‑γ at the transcriptional level; in addition, activation of PPAR‑γ upregulated visfatin at the mRNA and protein expression levels. Therefore, the PPAR‑γ signaling pathway may be involved in the regulation of visfatin by IL‑6 in BeWo cells. These results may provide novel insight into the roles of visfatin in trophoblastic cells. Furthermore, thiazolidinedione pioglitazone, by upregulating visfatin expression, may promote the energy metabolism of trophoblastic cells, maintain the function of the placenta and improve the outcome of pregnancy.

摘要

内脂素是一种脂肪细胞因子和胞质酶,具有烟酰胺磷酸核糖转移酶(Nampt)活性,参与多种代谢紊乱的发病机制。此外,核受体过氧化物酶体增殖物激活受体-γ(PPAR-γ)在抗炎反应中发挥重要作用,并调节葡萄糖和脂质代谢。本研究旨在探讨白细胞介素-6(IL-6)对BeWo 细胞内脂素表达和分泌的影响,并确定 PPAR-γ 途径是否参与 IL-6 对内脂素的调节。因此,用不同浓度的 IL-6 或吡格列酮刺激 BeWo 细胞,通过逆转录-定量聚合酶链反应和蛋白质印迹法测定内脂素和 PPAR-γ的表达水平。本研究结果表明,IL-6 下调了 visfatin 和 PPAR-γ 的 mRNA 水平,两者呈强相关性。吡格列酮激活 PPAR-γ 导致 visfatin 的表达显著增加,从而阻断了 IL-6 对 BeWo 细胞中 visfatin 的抑制作用。此外,与对照组或单独使用 IL-6 相比,单独使用吡格列酮可增加 visfatin 蛋白的表达和分泌。综上所述,本研究结果表明,IL-6 在转录水平上抑制 visfatin 和 PPAR-γ 的表达;此外,激活 PPAR-γ 可上调 visfatin 在 mRNA 和蛋白表达水平上的表达。因此,PPAR-γ 信号通路可能参与了 IL-6 对 BeWo 细胞内脂素的调节。这些结果可能为内脂素在滋养层细胞中的作用提供新的见解。此外,噻唑烷二酮吡格列酮通过上调内脂素的表达,可能促进滋养层细胞的能量代谢,维持胎盘的功能,改善妊娠结局。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd60/6297763/402301ac6b8e/MMR-19-01-0400-g00.jpg

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