辅酶Q-10可通过转化生长因子β3减少子宫肌瘤细胞外基质蛋白的异常生成。

F&S science Pub Date : 2024-11-01 DOI:10.1016/j.xfss.2024.07.004

Charlene Echague D.O. , Minnie Malik Ph.D. , Paul Driggers Ph.D. , William H. Catherino M.D., Ph.D.

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引用次数: 0

摘要

目的评估辅酶Q-10（CoQ-10）对子宫肌瘤中由转化生长因子β3（TGF-ß3）介导的细胞外基质蛋白合成失调的影响设计：实验室研究对象：无无用TGF-ß3和CoQ-10处理永生化子宫肌瘤和子宫肌瘤细胞：用TGF-ß3和浓度为10、50和100 μM的CoQ-10同时处理永生子宫肌瘤和子宫肌瘤细胞24小时后，通过Western印迹分析评估胶原1A1 (COL1A1)、胶原3A1 (COL3A1)、胶原11A1 (COL11A1)和纤连蛋白(FN1)的蛋白质浓度：结果：与未处理的细胞相比，暴露于 TGF-ß3 24 小时的永生化子宫肌瘤和子宫肌细胞显示出 COL1A1、COL3A1、COL11A1 和 FN1 的显著上调。与单独使用 TGF-ß3 处理的细胞相比，在相同时间内同时使用 CoQ-10 处理子宫肌瘤细胞时，这些蛋白质浓度会出现剂量依赖性下降。在 100 μM CoQ-10 的最高浓度下，观察到 COL1A1（0.59 + 0.10 倍，P = 0.03）、COL3A1（0.46 + 0.09 倍，P = 0.002）、COL11A1（0.53 + 0.09 倍，P = 0.01）和 FN1（0.56 + 0.09 倍，P = 0.002）的含量显著下降。同样，与单独暴露于 TGF-ß3 的细胞相比，同时暴露于 TGF-ß3 和 CoQ-10 的子宫肌细胞表现出细胞外基质蛋白量的剂量反应性下降。当 CoQ-10 浓度为 100 μM 时，COL1A1（0.75 + 0.03 倍，P = 0.03）、COL3A1（0.48 + 0.06 倍，P = 0.04）、COL11A1（0.38 + 0.06，P = 0.003）和 FN1（0.69 + 0.04 倍，P = 0.006）的含量显著减少：结论：CoQ-10能缓解TGF-ß3介导的子宫肌瘤细胞外基质关键生物标志物的异常生成。我们的研究结果表明，CoQ-10是一种很有前景的非激素化合物，它能对抗子宫肌瘤固有的纤维增生过程。

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

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.

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来源期刊

F&S science Endocrinology, Diabetes and Metabolism, Obstetrics, Gynecology and Women's Health, Urology

CiteScore

2.00

自引率

0.00%

发文量

审稿时长

51 days