MicroRNA-138 Suppresses Adipogenic Differentiation in Human Adipose Tissue-Derived Mesenchymal Stem Cells by Targeting Lipoprotein Lipase
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Purpose: Adipogenic differentiation of adipose tissue-derived mesenchymal stem cells (AMSCs) is critical to many disease-relateddisorders, 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-138and lipoprotein lipase (LPL), a key lipogenic enzyme, in AMSCs. Materials and Methods: Human AMSCs (hAMSCs) isolated from human abdomen tissue were subjected to adipogenic differentiationmedium. Quantitative real-time polymerase chain reaction and Western blot assay were applied to measure the expressionsof miR-138, LPL, and the two adipogenic transcription factors cytidine-cytidine-adenosine-adenosine-thymidine enhancerbinding 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. Duringadipogenesis of hAMSCs, miR-138 expression was significantly downregulated. Overexpression of miR-138 by transfection inhibitedhAMSCs adipogenic differentiation in vitro. Mechanically, LPL was a target of miR-138. LPL expression was upregulated duringadipogenesis of hAMSCs, and this upregulation was reversed by miR-138 overexpression. Functionally, silencing of LPL by transfectionexerted similar inhibition of the expressions of C/EBPα and PPARγ. Meanwhile, LPL ectopic expression was able to partlyabolish 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.
Abstract
Purpose: Adipogenic differentiation of adipose tissue-derived mesenchymal stem cells (AMSCs) is critical to many disease-relateddisorders, 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-138and lipoprotein lipase (LPL), a key lipogenic enzyme, in AMSCs. Materials and Methods: Human AMSCs (hAMSCs) isolated from human abdomen tissue were subjected to adipogenic differentiationmedium. Quantitative real-time polymerase chain reaction and Western blot assay were applied to measure the expressionsof miR-138, LPL, and the two adipogenic transcription factors cytidine-cytidine-adenosine-adenosine-thymidine enhancerbinding 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. Duringadipogenesis of hAMSCs, miR-138 expression was significantly downregulated. Overexpression of miR-138 by transfection inhibitedhAMSCs adipogenic differentiation in vitro. Mechanically, LPL was a target of miR-138. LPL expression was upregulated duringadipogenesis of hAMSCs, and this upregulation was reversed by miR-138 overexpression. Functionally, silencing of LPL by transfectionexerted similar inhibition of the expressions of C/EBPα and PPARγ. Meanwhile, LPL ectopic expression was able to partlyabolish 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.
참고문헌 (26)
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