Metformin as a potential agent for modulating the faulty endometriotic mesenchymal stem cells: A case-control study

سال انتشار: 1401
نوع سند: مقاله ژورنالی
زبان: انگلیسی
مشاهده: 46

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شناسه ملی سند علمی:

JR_IJRM-20-10_007

تاریخ نمایه سازی: 17 آبان 1401

چکیده مقاله:

Background: According to stem cell theory, it seems that the proliferation/differentiation imbalance in endometrial mesenchymal stem cells (eMSCs) is the leading cause of endometriosis, so targeting them to modulate stemness-relevant factors seems to be a wise choice for endometriosis treatment. Objective: We aimed to investigate the effects of metformin on stemness properties of eMSCs by evaluating the expression profile of stemness-related genes and microRNAs (miRNAs). Materials and Methods: In this case-control study, MSCs were isolated from the eutopic endometrium of ۳ endometriotic and ۳ healthy women. After their characterization and culture, they were treated with ۰.۱, ۱, and ۱۰ mM metformin for ۷۲ hr. Finally, the expression of octamer-binding transcription factor (OCT) ۴A, OCT۴B, OCT۴B۱, sex determining region Y-Box transcription factor ۲, nanog homeobox, microRNA-۲۰۰b, microRNA-۱۴۵, and lethal-۷b were analyzed by quantitative reverse transcription-polymerase chain reaction. Results: Metformin modulated the expression of stemness-related genes and miRNAs, OCT۴A, OCT۴B, OCT۴B۱, sex determining region Y-Box transcription factor ۲, nanog homeobox, microRNA-۲۰۰b, microRNA-۱۴۵, and lethal-۷b in eMSCs, especially at ۱ and ۱۰ mM concentration. Notably, metformin had a paradoxical effect on normal eMSCs. Conclusion: We showed that metformin could modulate the expression of deregulated genes and miRNAs in faulty eMSCs, and restore their skewed self-renewal/differentiation balance, so it might be a promising drug for endometriosis treatment. The paradoxical effect of metformin on eMSCs and normal eMSCs might be because of their different metabolic patterns, so it requires further investigation to illustrate.

نویسندگان

Parisa Mashayekhi

Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

Mehrdad Noruzinia

Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Sepideh Khodaverdi

Endometriosis Research Center, Iran University of Medical Sciences, Tehran, Iran.

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