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二甲双胍和维生素 D 调控脂肪干细胞成脂分化：miRNAs 的作用。

Tuning Adipogenic Differentiation in ADSCs by Metformin and Vitamin D: Involvement of miRNAs.

机构信息

Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy.

Department of Medical, Surgical and Experimental Sciences, General Surgery Unit 2 "Clinica Chirurgica", University of Sassari, Viale San Pietro 8, 07100 Sassari, Italy.

出版信息

Int J Mol Sci. 2020 Aug 27;21(17):6181. doi: 10.3390/ijms21176181.

DOI:10.3390/ijms21176181
PMID:32867201
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7504286/
Abstract

Fat tissue represents an important source of adipose-derived stem cells (ADSCs), which can differentiate towards several phenotypes under certain stimuli. Definite molecules as vitamin D are able to influence stem cell fate, acting on the expression of specific genes. In addition, miRNAs are important modulating factors in obesity and numerous diseases. We previously identified specific conditioned media able to commit stem cells towards defined cellular phenotypes. In the present paper, we aimed at evaluating the role of metformin on ADSCs differentiation. In particular, ADSCs were cultured in a specific adipogenic conditioned medium (MD), in the presence of metformin, alone or in combination with vitamin D. Our results showed that the combination of the two compounds is able to counteract the appearance of an adipogenic phenotype, indicating a feedforward regulation on vitamin D metabolism by metformin, acting on CYP27B1 and CYP3A4. We then evaluated the role of specific epigenetic modulating genes and miRNAs in controlling stem cell adipogenesis. The combination of the two molecules was able to influence stem cell fate, by modulating the adipogenic phenotype, suggesting their possible application in clinical practice in counteracting uncontrolled lipogenesis and obesity-related diseases.

摘要

脂肪组织是脂肪来源干细胞（ADSCs）的重要来源，在某些刺激下，ADSCs 可以向几种表型分化。某些确定的分子，如维生素 D，能够影响干细胞命运，作用于特定基因的表达。此外，miRNAs 是肥胖和许多疾病的重要调节因子。我们之前已经确定了特定的条件培养基，能够使干细胞向特定的细胞表型分化。在本文中，我们旨在评估二甲双胍对 ADSCs 分化的作用。具体来说，ADSCs 在特定的成脂条件培养基（MD）中培养，单独或与维生素 D 联合使用二甲双胍。我们的结果表明，这两种化合物的组合能够抵消脂肪生成表型的出现，表明二甲双胍通过作用于 CYP27B1 和 CYP3A4 对维生素 D 代谢进行前馈调节。然后，我们评估了特定的表观遗传调节基因和 miRNAs 在控制干细胞成脂分化中的作用。这两种分子的组合能够通过调节脂肪生成表型来影响干细胞命运，提示它们在临床上可能用于对抗不受控制的脂肪生成和肥胖相关疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f665/7504286/86eaeba7a748/ijms-21-06181-g007.jpg
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