Epigallocatechine-3-gallate Inhibits the Adipogenesis of Human Mesenchymal Stem Cells via the Regulation of Protein Phosphatase-2A and Myosin Phosphatase
Epigallocatechin-3-gallate (EGCG) has widespread effects on adipocyte development. However, the molecular mechanisms of EGCG are not fully understood. We investigate the adipogenic differentiation of human-derived mesenchymal stem cells, including lipid deposition and changes in the expression and p...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-05-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/11/10/1704 |
| _version_ | 1797500874027696128 |
|---|---|
| author | Bálint Bécsi Zoltán Kónya Anita Boratkó Katalin Kovács Ferenc Erdődi |
| author_facet | Bálint Bécsi Zoltán Kónya Anita Boratkó Katalin Kovács Ferenc Erdődi |
| author_sort | Bálint Bécsi |
| collection | DOAJ |
| description | Epigallocatechin-3-gallate (EGCG) has widespread effects on adipocyte development. However, the molecular mechanisms of EGCG are not fully understood. We investigate the adipogenic differentiation of human-derived mesenchymal stem cells, including lipid deposition and changes in the expression and phosphorylation of key transcription factors, myosin, protein phosphatase-2A (PP2A), and myosin phosphatase (MP). On day 6 of adipogenic differentiation, EGCG (1–20 µM) suppressed lipid droplet formation, which was counteracted by an EGCG-binding peptide for the 67 kDa laminin receptor (67LR), suggesting that EGCG acts via 67LR. EGCG decreased the phosphorylation of CCAAT-enhancer-binding protein beta via the activation of PP2A in a protein kinase A (PKA)-dependent manner, leading to the partial suppression of peroxisome proliferator-activated receptor gamma (PPARγ) and adiponectin expression. Differentiated cells exhibited a rounded shape, cortical actin filaments, and lipid accumulation. The EGCG treatment induced cell elongation, stress fiber formation, and less lipid accumulation. These effects were accompanied by the degradation of the MP target subunit-1 and increased the phosphorylation of the 20 kDa myosin light chain. Our results suggest that EGCG acts as an agonist of 67LR to inhibit adipogenesis via the activation of PP2A and suppression of MP. These events are coupled with the decreased phosphorylation and expression levels of adipogenic transcription factors and changes in cell shape, culminating in curtailed adipogenesis. |
| first_indexed | 2024-03-10T03:10:08Z |
| format | Article |
| id | doaj.art-e144a3af52f14707846924b15de3fc28 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T03:10:08Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-e144a3af52f14707846924b15de3fc282023-11-23T10:28:28ZengMDPI AGCells2073-44092022-05-011110170410.3390/cells11101704Epigallocatechine-3-gallate Inhibits the Adipogenesis of Human Mesenchymal Stem Cells via the Regulation of Protein Phosphatase-2A and Myosin PhosphataseBálint Bécsi0Zoltán Kónya1Anita Boratkó2Katalin Kovács3Ferenc Erdődi4Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Medical Chemistry, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Medical Chemistry, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Medical Chemistry, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Medical Chemistry, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryEpigallocatechin-3-gallate (EGCG) has widespread effects on adipocyte development. However, the molecular mechanisms of EGCG are not fully understood. We investigate the adipogenic differentiation of human-derived mesenchymal stem cells, including lipid deposition and changes in the expression and phosphorylation of key transcription factors, myosin, protein phosphatase-2A (PP2A), and myosin phosphatase (MP). On day 6 of adipogenic differentiation, EGCG (1–20 µM) suppressed lipid droplet formation, which was counteracted by an EGCG-binding peptide for the 67 kDa laminin receptor (67LR), suggesting that EGCG acts via 67LR. EGCG decreased the phosphorylation of CCAAT-enhancer-binding protein beta via the activation of PP2A in a protein kinase A (PKA)-dependent manner, leading to the partial suppression of peroxisome proliferator-activated receptor gamma (PPARγ) and adiponectin expression. Differentiated cells exhibited a rounded shape, cortical actin filaments, and lipid accumulation. The EGCG treatment induced cell elongation, stress fiber formation, and less lipid accumulation. These effects were accompanied by the degradation of the MP target subunit-1 and increased the phosphorylation of the 20 kDa myosin light chain. Our results suggest that EGCG acts as an agonist of 67LR to inhibit adipogenesis via the activation of PP2A and suppression of MP. These events are coupled with the decreased phosphorylation and expression levels of adipogenic transcription factors and changes in cell shape, culminating in curtailed adipogenesis.https://www.mdpi.com/2073-4409/11/10/1704mesenchymal stem cellsadipogenesisepigallocatechin-3-gallate (EGCG)67 kDa laminin receptor (67LR)protein phosphatase-2A (PP2A)myosin phosphatase |
| spellingShingle | Bálint Bécsi Zoltán Kónya Anita Boratkó Katalin Kovács Ferenc Erdődi Epigallocatechine-3-gallate Inhibits the Adipogenesis of Human Mesenchymal Stem Cells via the Regulation of Protein Phosphatase-2A and Myosin Phosphatase Cells mesenchymal stem cells adipogenesis epigallocatechin-3-gallate (EGCG) 67 kDa laminin receptor (67LR) protein phosphatase-2A (PP2A) myosin phosphatase |
| title | Epigallocatechine-3-gallate Inhibits the Adipogenesis of Human Mesenchymal Stem Cells via the Regulation of Protein Phosphatase-2A and Myosin Phosphatase |
| title_full | Epigallocatechine-3-gallate Inhibits the Adipogenesis of Human Mesenchymal Stem Cells via the Regulation of Protein Phosphatase-2A and Myosin Phosphatase |
| title_fullStr | Epigallocatechine-3-gallate Inhibits the Adipogenesis of Human Mesenchymal Stem Cells via the Regulation of Protein Phosphatase-2A and Myosin Phosphatase |
| title_full_unstemmed | Epigallocatechine-3-gallate Inhibits the Adipogenesis of Human Mesenchymal Stem Cells via the Regulation of Protein Phosphatase-2A and Myosin Phosphatase |
| title_short | Epigallocatechine-3-gallate Inhibits the Adipogenesis of Human Mesenchymal Stem Cells via the Regulation of Protein Phosphatase-2A and Myosin Phosphatase |
| title_sort | epigallocatechine 3 gallate inhibits the adipogenesis of human mesenchymal stem cells via the regulation of protein phosphatase 2a and myosin phosphatase |
| topic | mesenchymal stem cells adipogenesis epigallocatechin-3-gallate (EGCG) 67 kDa laminin receptor (67LR) protein phosphatase-2A (PP2A) myosin phosphatase |
| url | https://www.mdpi.com/2073-4409/11/10/1704 |
| work_keys_str_mv | AT balintbecsi epigallocatechine3gallateinhibitstheadipogenesisofhumanmesenchymalstemcellsviatheregulationofproteinphosphatase2aandmyosinphosphatase AT zoltankonya epigallocatechine3gallateinhibitstheadipogenesisofhumanmesenchymalstemcellsviatheregulationofproteinphosphatase2aandmyosinphosphatase AT anitaboratko epigallocatechine3gallateinhibitstheadipogenesisofhumanmesenchymalstemcellsviatheregulationofproteinphosphatase2aandmyosinphosphatase AT katalinkovacs epigallocatechine3gallateinhibitstheadipogenesisofhumanmesenchymalstemcellsviatheregulationofproteinphosphatase2aandmyosinphosphatase AT ferencerdodi epigallocatechine3gallateinhibitstheadipogenesisofhumanmesenchymalstemcellsviatheregulationofproteinphosphatase2aandmyosinphosphatase |