分泌型Frizzled相关蛋白5在微囊藻-亮氨酸-精氨酸诱导的小鼠肝脂代谢紊乱中介导Wnt5a的表达

Mei Yan Yang, Fu Rong Yu, Qian Qian Ji, Hui Ying Zhang, Jia Xiang Zhang, Dao Jun Chen
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引用次数: 0

摘要

目的微囊藻毒素-亮氨酸-精氨酸(MC-LR)暴露会诱发肝脏脂质代谢紊乱。分泌的褐飞虱相关蛋白 5(SFRP5)是翼型 MMTV 整合位点家族 5A 成员(Wnt5a)的天然拮抗剂,也是一种抗炎性脂肪细胞因子。本研究旨在探讨 MC-LR 是否能诱导肝细胞脂质代谢紊乱,以及具有抗炎作用的 SFRP5 是否能通过抑制 Wnt5a/Jun N-terminal kinase(JNK)通路减轻肝脂质代谢紊乱的影响:方法:我们让小鼠体内暴露于 MC-LR 以诱导肝脏脂质代谢紊乱。随后,将过表达或不表达 SFRP5 的小鼠肝细胞暴露于 MC-LR,观察 SFRP5 过表达对 MC-LR 引起的炎症和 Wnt5a/JNK 激活的影响:结果:暴露于MC-LR会诱发小鼠肝脏脂质代谢紊乱,并以浓度依赖性方式显著降低SFRP5 mRNA和蛋白水平。在 AML12 细胞中过表达 SFRP5 可抑制 MC-LR 诱导的炎症。过表达 SFRP5 还能抑制 Wnt5a 和 JNK 的磷酸化:结论:MC-LR可诱导小鼠脂质代谢紊乱,而SFRP5可通过抑制Wnt5a/JNK信号转导减轻小鼠肝脏脂质代谢紊乱。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Secreted Frizzled-Related Protein 5 Mediates Wnt5a Expression in Microcystin-Leucine-Arginine-Induced Liver Lipid Metabolism Disorder in Mice.

Objective: Microcystin-leucine-arginine (MC-LR) exposure induces lipid metabolism disorders in the liver. Secreted frizzled-related protein 5 (SFRP5) is a natural antagonist of winglesstype MMTV integration site family, member 5A (Wnt5a) and an anti-inflammatory adipocytokine. In this study, we aimed to investigate whether MC-LR can induce lipid metabolism disorders in hepatocytes and whether SFRP5, which has anti-inflammatory effects, can alleviate the effects of hepatic lipid metabolism by inhibiting the Wnt5a/Jun N-terminal kinase (JNK) pathway.

Methods: We exposed mice to MC-LR in vivo to induce liver lipid metabolism disorders. Subsequently, mouse hepatocytes that overexpressed SFRP5 or did not express SFRP5 were exposed to MC-LR, and the effects of SFRP5 overexpression on inflammation and Wnt5a/JNK activation by MC-LR were observed.

Results: MC-LR exposure induced liver lipid metabolism disorders in mice and significantly decreased SFRP5 mRNA and protein levels in a concentration-dependent manner. SFRP5 overexpression in AML12 cells suppressed MC-LR-induced inflammation. Overexpression of SFRP5 also inhibited Wnt5a and phosphorylation of JNK.

Conclusion: MC-LR can induce lipid metabolism disorders in mice, and SFRP5 can attenuate lipid metabolism disorders in the mouse liver by inhibiting Wnt5a/JNK signaling.

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