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通过调节MKK7/JNK/c-Jun信号通路对骨髓来源的人间充质干细胞死亡信号的保护作用。

Protective Effects of - on Cell Death Signals on the Bone Marrow-Derived Human Mesenchymal Stem Cells via Regulation of MKK7/JNK/c-Jun Signaling Pathway.

作者信息

Yoon Hee-Jae, Cho Si-Yoon, Kim Hyeong-Geug, Lee Ji-Yeon

机构信息

Department of Obstetrics and Gynecology, College of Korean Medicine, Daejeon University, Daejeon, Republic of Korea.

Department of Leukopak Research and Developement, QPS Bio-Kinetic, Springfield, MO, USA.

出版信息

J Pharmacopuncture. 2024 Jun 30;27(2):131-141. doi: 10.3831/KPI.2024.27.2.131.

Abstract

OBJECTIVES

Polycystic ovary syndrome (PCOS) is one of the most common disorders and it shows up to 20% prevalence in reproductive-aged women populations, but no cures are available to date. We aimed to investigate the protective effects of (CBD) on cell death signaling pathways, inflammation, and oxidative stress observed in Bone-Marrow derived human mesenchymal stem cell (BM-hMSC) by means of PCOS therapeutics in the future.

METHODS

BM-hMSCs were applied with cell deaths and injuries. Apoptosis and pyroptosis signals were quenched with their related signaling pathways using quantitative PCR, Western blot, and fluorescence image analysis.

RESULTS

Our data clearly displayed hydrogen peroxide- and nigericin-treated cell death signaling pathways via regulations of mitochondrial integrity and interleukin (IL)-1β at the cellular levels (p < 0.01 or 0.001). We further observed that pre-treatment with CBD showed protective effects against oxidative stress by enhancement of antioxidant components at the cellular level, with respect to both protein and mRNA expression levels (p < 0.05, 0.01 or 0.001). The mechanisms of CBD were examined by Western blot analysis, and it showed anti-cell death, anti-inflammatory, and antioxidant effects via normalizations of the Jun N-terminal kinase/mitogen-activated protein kinase kinase 7/c-Jun signaling pathways.

CONCLUSION

This study confirmed the pharmacological properties of CBD by regulation of cellular oxidation and the inflammation-provoked cell death condition of BM-hMSCs, which is mediated by the MKK7/JNK/c-Jun signaling pathway.

摘要

目的

多囊卵巢综合征(PCOS)是最常见的疾病之一,在育龄女性人群中的患病率高达20%,但迄今为止尚无治愈方法。我们旨在研究大麻二酚(CBD)对骨髓来源的人间充质干细胞(BM-hMSC)中观察到的细胞死亡信号通路、炎症和氧化应激的保护作用,以期未来用于PCOS的治疗。

方法

对BM-hMSCs施加细胞死亡和损伤。使用定量PCR、蛋白质印迹法和荧光图像分析,通过相关信号通路淬灭凋亡和焦亡信号。

结果

我们的数据清楚地显示,在细胞水平上,过氧化氢和尼日利亚菌素处理的细胞死亡信号通路是通过线粒体完整性和白细胞介素(IL)-1β的调节实现的(p<0.01或0.001)。我们进一步观察到,CBD预处理在细胞水平上通过增强抗氧化成分对氧化应激具有保护作用,在蛋白质和mRNA表达水平方面均如此(p<0.05、0.01或0.001)。通过蛋白质印迹分析研究了CBD的作用机制,结果显示其通过使Jun N端激酶/丝裂原活化蛋白激酶激酶7/c-Jun信号通路正常化而具有抗细胞死亡、抗炎和抗氧化作用。

结论

本研究通过调节细胞氧化和由MKK7/JNK/c-Jun信号通路介导引发的BM-hMSCs炎症性细胞死亡状态,证实了CBD的药理特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06b9/11194519/d5f5348e1429/jop-27-2-131-f1.jpg

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