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

Autor:	Echague C; 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., Malik M; Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland., Driggers P; Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland., Catherino WH; 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. Electronic address: william.catherino@usuhs.edu.
Jazyk:	angličtina
Zdroj:	F&S science [F S Sci] 2024 Nov; Vol. 5 (4), pp. 342-351. Date of Electronic Publication: 2024 Jul 14.
DOI:	10.1016/j.xfss.2024.07.004
Abstrakt:	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. Competing Interests: Declaration of Interests C.E. reports funding from the Military Women’s Health Research Grant, Uniformed Services University of the Health Sciences, for the submitted work; and travel support from the US Fertility, outside the submitted work. M.M. reports funding from the Military Women’s Health Research Grant, Uniformed Services University of the Health Sciences, for the submitted work. P.D. reports funding from the Military Women’s Health Research Grant, Uniformed Services University of the Health Sciences, for the submitted work. W.H.C. reports consulting fees from Bayer and Sumitomo Pharma; and is Chair of the Scholar Committee of the American Association of Obstetricians and Gynecologists Foundation; Division Director, Reproductive Endocrinology and Infertility, American Board of Obstetrics and Gynecology; Editor-in-Chief of F&S Science, American Society for Reproductive Medicine; and spouse is the Head of US Medical Affairs, Fertility and Endocrinology, EMD Serono. (Published by Elsevier Inc.)
Databáze:	MEDLINE
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