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مقالات فارسیISIکنفرانسهاژورنالها

Effect of miR-۱۸a-۵p, miR-۱۹a-۳p, and miR-۲۰a-۵p on In Vitro Cardiomyocyte Differentiation of Human Endometrium Tissue-Derived Stem Cells Through Regulation of Smad۴ Expression

محل انتشار: مجله گزارش های بیوشیمی و زیست شناسی مولکولی، دوره: 12، شماره: 1
سال انتشار: 1402
نوع سند: مقاله ژورنالی
زبان: انگلیسی
مشاهده: 80

فایل این مقاله در 11 صفحه با فرمت PDF قابل دریافت می باشد

استخراج به نرم افزارهای پژوهشی:

لینک ثابت به این مقاله:
https://civilica.com/doc/1735989

شناسه ملی سند علمی:

JR_RBMB-12-1_014

تاریخ نمایه سازی: 31 مرداد 1402

چکیده مقاله:

Background: Smad۴ regulates the expression of the genes required for heart homeostasis. Regarding the central role of microRNAs in cardiac biology, we investigated the expression of the three Smad۴-targeting miRNAs, namely miR-۱۸a-۵p, miR-۱۹a-۳p, and miR-۲۰a-۵p, as well as Smad۴ during differentiation of human endometrium-derived mesenchymal stem cells (hEMSCs) into cardiomyocytes (CMs). Methods: To evaluate mesenchymal phenotype and multi-lineage differentiation ability of hEMSCs, immunophenotyping by flow cytometry and differentiation into osteoblasts and adipocytes were performed, respectively. For transdifferentiation into CMs, hEMSCs were exposed to a cardiomyogenic medium composed of ۵-aza and bFGF for ۳۰ days. The comparison between transcriptional expression levels of Nkx۲-۵, GATA۴, Smad۴, TNNT۲, TBX۵, miR-۱۸a-۵p, miR-۱۹a-۳p, and miR-۲۰a-۵p by qRT-PCR, as well as protein levels of Nkx۲-۵, Smad۴, and cTnT by immunofluorescence staining, was conducted in every ۶ days. Results: In vitro, the mesenchymal stem cell phenotype of hEMSCs and their potency for differentiation into other MSCs were confirmed. Differentiated hEMSCs had morphological characteristics of CMs. The percentage of positive cells for Nkx۲-۵, Smad۴, and cTnT proteins was increased following induction and culminated on the ۲۴th day. Also, mRNA levels of Nkx۲-۵, GATA۴, Smad۴, TNNT۲, and TBX۵ exhibited the same trend. The expression of investigated miRNAs was significantly decreased sequentially. A significant negative correlation between expressions of Smad۴ and investigated miRNAs was observed. Conclusions: Our results indicate that miR-۱۸a-۵p, miR-۱۹a-۳p, and miR-۲۰a-۵p are involved in the cardiac differentiation propensity of hEMSCs potentially by regulation of Smad levels. Although, more mechanistic experiments are required to confirm this idea.

کلیدواژه ها:

Endometrium-derived mesenchymal stem cells (EMSCs) ، miR-۱۸a-۵p ، miR-۱۹a-۳p ، miR-۲۰a-۵p ، Smad۴.

نویسندگان

Behnaz Maleki

Physiology Research Center, Kashan University of Medical Sciences, Kashan, Iran.

Mahdi Noureddini

Physiology Research Center, Kashan University of Medical Sciences, Kashan, Iran & Department of Applied Cell Sciences, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran.

Somayeh Saadat

Physiology Research Center, Kashan University of Medical Sciences, Kashan, Iran.

Javad Verdi

Department of Applied Cellular Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Alireza Farrokhian

Department of Cardiology, School of Medicine, Shahid Beheshti Hospital, Kashan University of Medical Sciences, Kashan, Iran.

Hossein Ghanbarian

Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Ebrahim Cheraghi

Department of Biology, Faculty of Science, University of Qom, Qom, Iran.

Behrang Alani

Department of Applied Cell Sciences, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran.

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