MicroRNA-138 Suppresses Adipogenic Differentiation in Human Adipose Tissue-Derived Mesenchymal Stem Cells by Targeting Lipoprotein Lipase
10.3349/ymj.2019.60.12.1187
- Author:
Yuting WANG
1
;
Lixin LIN
;
Yong HUANG
;
Junjun SUN
;
Xueming WANG
;
Peng WANG
Author Information
1. Department of Burn Plastic Surgery, the Yuhuangding Hospital of Yantai, Yantai, China. zydmbp@163.com
- Publication Type:Original Article
- Keywords:
miR-138;
adipogenic differentiation;
hAMSCs;
lipoprotein lipase (LPL)
- MeSH:
Abdomen;
Adipogenesis;
Blotting, Western;
Carrier Proteins;
Ectopic Gene Expression;
Humans;
In Vitro Techniques;
Lipoprotein Lipase;
Lipoproteins;
Luciferases;
Mesenchymal Stromal Cells;
Obesity;
PPAR gamma;
Real-Time Polymerase Chain Reaction;
Transcription Factors;
Transfection;
Up-Regulation
- From:Yonsei Medical Journal
2019;60(12):1187-1194
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: Adipogenic differentiation of adipose tissue-derived mesenchymal stem cells (AMSCs) is critical to many disease-related disorders, such as obesity and diabetes. Studies have demonstrated that miRNA-138 (miR-138) is closely involved in adipogenesis. However, the mechanisms affected by miR-138 remain unclear. This work aimed to investigate interactions between miR-138 and lipoprotein lipase (LPL), a key lipogenic enzyme, in AMSCs. MATERIALS AND METHODS: Human AMSCs (hAMSCs) isolated from human abdomen tissue were subjected to adipogenic differentiation medium. Quantitative real-time polymerase chain reaction and Western blot assay were applied to measure the expressions of miR-138, LPL, and the two adipogenic transcription factors cytidine-cytidine-adenosine-adenosine-thymidine enhancer binding protein alpha (C/EBPα) and peroxisome proliferator-activated receptor gamma (PPARγ). The relationship between miR-138 and LPL was predicted utilizing the miRTarBase database and validated by dual luciferase reporter assay. RESULTS: Showing increases in C/EBPα and PPARγ expression levels, hAMSCs were induced into adipogenic differentiation. During adipogenesis of hAMSCs, miR-138 expression was significantly downregulated. Overexpression of miR-138 by transfection inhibited hAMSCs adipogenic differentiation in vitro. Mechanically, LPL was a target of miR-138. LPL expression was upregulated during adipogenesis of hAMSCs, and this upregulation was reversed by miR-138 overexpression. Functionally, silencing of LPL by transfection exerted similar inhibition of the expressions of C/EBPα and PPARγ. Meanwhile, LPL ectopic expression was able to partly abolish the suppressive effect of miR-138 overexpression on adipogenic differentiation of hAMSCs. CONCLUSION: Upregulation of miR-138 inhibits adipogenic differentiation of hAMSCs by directly downregulating LPL.
