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辅酶 Q-10 通过转化生长因子β3 减少了子宫平滑肌瘤中细胞外基质蛋白的异常产生。

Coenzyme Q-10 reduced the aberrant production of extracellular matrix proteins in uterine leiomyomas through transforming growth factor beta 3.

机构信息

Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland; Program in Reproductive Endocrinology and Gynecology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.

Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland.

出版信息

F S Sci. 2024 Nov;5(4):342-351. doi: 10.1016/j.xfss.2024.07.004. Epub 2024 Jul 14.

Abstract

OBJECTIVE

To evaluate the impact of coenzyme Q-10 (CoQ-10) on the dysregulated synthesis of extracellular matrix proteins mediated by transforming growth factor beta 3 (TGF-β3) in uterine leiomyomas.

DESIGN

Laboratory study.

SETTING

University.

PATIENTS

None.

INTERVENTIONS

Treatment of immortalized uterine myometrial and leiomyoma cells to TGF-β3 and CoQ-10.

MAIN OUTCOME MEASURES

The protein concentrations of collagen 1A1 (COL1A1), collagen 3A1 (COL3A1), collagen 11A1 (COL11A1), and fibronectin (FN1) were assessed through western blot analysis after treatment of immortalized uterine myometrial and leiomyoma cells with both transforming growth factor beta (TGF-β) 3 and concentrations of CoQ-10 at 10, 50, and 100 μM concurrently for 24 hours.

RESULTS

Immortalized uterine leiomyoma and myometrial cells exposed to TGF-β3 for 24 hours demonstrated a significant up-regulation of COL1A1, COL3A1, COL11A1, and FN1 compared with untreated cells. In leiomyoma cells, concurrent treatment with CoQ-10 over the same timeframe revealed a dose-dependent decrease in these protein concentrations compared with those in cells treated with TGF-β3 alone. At the highest concentration of 100 μM of CoQ-10, significant decreases in the amounts of COL1A1 (0.59 ± 0.10-fold), COL3A1 (0.46 ± 0.09-fold), COL11A1 (0.53 ± 0.09-fold), and FN1 (0.56 ± 0.09-fold) were observed. Similarly, myometrial cells exposed to both TGF-β3 and CoQ-10 demonstrated a dose-responsive decline in the amount of extracellular matrix protein compared with cells exposed to TGF-β3 alone. Significant reductions in the amounts of COL1A1 (0.75 ± 0.03-fold), COL3A1 (0.48 ± 0.06-fold), COL11A1 (0.38 ± 0.06), and FN1 (0.69 ± 0.04-fold) were appreciated at 100-μM CoQ-10.

CONCLUSION

Coenzyme Q-10 mitigated the aberrant production of key biomarkers of the extracellular matrix mediated by TGF-β3 in uterine leiomyomas. Our findings highlight a promising nonhormonal compound that can counteract the fibroproliferative process inherent to leiomyomas.

摘要

目的

评估辅酶 Q-10(CoQ-10)对转化生长因子β3(TGF-β3)介导的细胞外基质蛋白失调合成的影响。

设计

实验室研究。

地点

大学。

患者

无。

干预措施

用 TGF-β3 和 CoQ-10 处理永生化子宫平滑肌细胞和子宫肌瘤细胞。

主要观察指标

用转化生长因子β(TGF-β)3 和 CoQ-10 浓度(10、50 和 100 μM)处理永生化子宫平滑肌细胞和子宫肌瘤细胞 24 小时后,通过 Western blot 分析评估胶原蛋白 1A1(COL1A1)、胶原蛋白 3A1(COL3A1)、胶原蛋白 11A1(COL11A1)和纤维连接蛋白(FN1)的蛋白浓度。

结果

与未处理的细胞相比,暴露于 TGF-β3 24 小时的永生化子宫肌瘤和子宫平滑肌细胞中 COL1A1、COL3A1、COL11A1 和 FN1 的表达显著上调。在子宫肌瘤细胞中,与单独用 TGF-β3 处理的细胞相比,在相同时间内用 CoQ-10 进行治疗时,这些蛋白浓度呈剂量依赖性下降。在用 100 μM CoQ-10 进行最高浓度处理时,观察到 COL1A1(0.59±0.10 倍)、COL3A1(0.46±0.09 倍)、COL11A1(0.53±0.09 倍)和 FN1(0.56±0.09 倍)的量显著减少。同样,与单独用 TGF-β3 处理的细胞相比,暴露于 TGF-β3 和 CoQ-10 的子宫平滑肌细胞的细胞外基质蛋白量也呈现出剂量反应性下降。在 100 μM CoQ-10 时,COL1A1(0.75±0.03 倍)、COL3A1(0.48±0.06 倍)、COL11A1(0.38±0.06)和 FN1(0.69±0.04 倍)的量明显减少。

结论

辅酶 Q-10 减轻了 TGF-β3 在子宫肌瘤中介导的细胞外基质关键生物标志物的异常产生。我们的发现强调了一种有前途的非激素化合物,可以对抗子宫肌瘤固有的纤维增生过程。

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