The Effect of TGFβ1 in Adipocyte on Inflammatory and Fibrotic Markers at Different Stages of Adipocyte Differentiation
Transforming growth factor beta (TGFβ) is a versatile cytokine. Although a profibrotic role of TGFβ is well established, its effect on tissue inhibitor of metalloproteinase (TIMPs) and inflammatory mediators are incompletely described. This study investigates the profibrotic and pro-inflammatory rol...
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MDPI AG
2022-11-01
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| Series: | Pathophysiology |
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| Online Access: | https://www.mdpi.com/1873-149X/29/4/50 |
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| author | Babu Raja Maharjan Susan V. McLennan Stephen M. Twigg Paul F. Williams |
| author_facet | Babu Raja Maharjan Susan V. McLennan Stephen M. Twigg Paul F. Williams |
| author_sort | Babu Raja Maharjan |
| collection | DOAJ |
| description | Transforming growth factor beta (TGFβ) is a versatile cytokine. Although a profibrotic role of TGFβ is well established, its effect on tissue inhibitor of metalloproteinase (TIMPs) and inflammatory mediators are incompletely described. This study investigates the profibrotic and pro-inflammatory role of TGFβ1 during adipocyte differentiation. NIH3T3L1 cells were used for the in vitro study and were differentiated by adding a standard differentiation mix either with rosiglitazone (R-Diff) or without (S-Diff). Recombinant TGFβ1 (2 ng/mL) was added to the undifferentiated preadipocyte during the commitment stage and at the terminal differentiation stage. TGFβ1 treatment significantly decreased adiponectin mRNA at both early commitment (>300 fold) and terminal differentiated cells [S-Diff (~33%) or R-Diff (~20%)]. TGFβ1 upregulated collagen VI mRNA and its regulators connective tissue growth factor (CCN2/CTGF), TIMP1 and TIMP3 mRNA levels in undifferentiated preadipocytes and adipocytes at commitment stage. But in the terminal differentiated adipocytes, changes in mRNA and protein of collagen VI and TIMP3 mRNA were not observed despite an increase in CCN2/CTGF, TIMP1 mRNA. Although TGFβ1 upregulated interleukin-6 (IL6) and monocyte chemoattractant protein-1 (MCP1) mRNA at all stages of differentiation, decreased tumor necrosis factor-α (TNFα) mRNA was observed early in adipocyte differentiation. This study highlights the complex role of TGFβ1 on extracellular matrix (ECM) remodeling and inflammatory markers in stimulating both synthetic and inhibitory markers of fibrosis at different stages of adipocyte differentiation. |
| first_indexed | 2024-03-09T15:59:38Z |
| format | Article |
| id | doaj.art-b47f6226446c4a728c748ae5b45a6e2b |
| institution | Directory Open Access Journal |
| issn | 1873-149X |
| language | English |
| last_indexed | 2024-03-09T15:59:38Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathophysiology |
| spelling | doaj.art-b47f6226446c4a728c748ae5b45a6e2b2023-11-24T17:14:55ZengMDPI AGPathophysiology1873-149X2022-11-0129464064910.3390/pathophysiology29040050The Effect of TGFβ1 in Adipocyte on Inflammatory and Fibrotic Markers at Different Stages of Adipocyte DifferentiationBabu Raja Maharjan0Susan V. McLennan1Stephen M. Twigg2Paul F. Williams3Greg Brown Diabetes & Endocrinology Laboratory, Sydney Medical School, University of Sydney, Sydney, NSW 2006, AustraliaGreg Brown Diabetes & Endocrinology Laboratory, Sydney Medical School, University of Sydney, Sydney, NSW 2006, AustraliaGreg Brown Diabetes & Endocrinology Laboratory, Sydney Medical School, University of Sydney, Sydney, NSW 2006, AustraliaGreg Brown Diabetes & Endocrinology Laboratory, Sydney Medical School, University of Sydney, Sydney, NSW 2006, AustraliaTransforming growth factor beta (TGFβ) is a versatile cytokine. Although a profibrotic role of TGFβ is well established, its effect on tissue inhibitor of metalloproteinase (TIMPs) and inflammatory mediators are incompletely described. This study investigates the profibrotic and pro-inflammatory role of TGFβ1 during adipocyte differentiation. NIH3T3L1 cells were used for the in vitro study and were differentiated by adding a standard differentiation mix either with rosiglitazone (R-Diff) or without (S-Diff). Recombinant TGFβ1 (2 ng/mL) was added to the undifferentiated preadipocyte during the commitment stage and at the terminal differentiation stage. TGFβ1 treatment significantly decreased adiponectin mRNA at both early commitment (>300 fold) and terminal differentiated cells [S-Diff (~33%) or R-Diff (~20%)]. TGFβ1 upregulated collagen VI mRNA and its regulators connective tissue growth factor (CCN2/CTGF), TIMP1 and TIMP3 mRNA levels in undifferentiated preadipocytes and adipocytes at commitment stage. But in the terminal differentiated adipocytes, changes in mRNA and protein of collagen VI and TIMP3 mRNA were not observed despite an increase in CCN2/CTGF, TIMP1 mRNA. Although TGFβ1 upregulated interleukin-6 (IL6) and monocyte chemoattractant protein-1 (MCP1) mRNA at all stages of differentiation, decreased tumor necrosis factor-α (TNFα) mRNA was observed early in adipocyte differentiation. This study highlights the complex role of TGFβ1 on extracellular matrix (ECM) remodeling and inflammatory markers in stimulating both synthetic and inhibitory markers of fibrosis at different stages of adipocyte differentiation.https://www.mdpi.com/1873-149X/29/4/50TGFβadipocytestages of differentiationinflammationfibrosis |
| spellingShingle | Babu Raja Maharjan Susan V. McLennan Stephen M. Twigg Paul F. Williams The Effect of TGFβ1 in Adipocyte on Inflammatory and Fibrotic Markers at Different Stages of Adipocyte Differentiation Pathophysiology TGFβ adipocyte stages of differentiation inflammation fibrosis |
| title | The Effect of TGFβ1 in Adipocyte on Inflammatory and Fibrotic Markers at Different Stages of Adipocyte Differentiation |
| title_full | The Effect of TGFβ1 in Adipocyte on Inflammatory and Fibrotic Markers at Different Stages of Adipocyte Differentiation |
| title_fullStr | The Effect of TGFβ1 in Adipocyte on Inflammatory and Fibrotic Markers at Different Stages of Adipocyte Differentiation |
| title_full_unstemmed | The Effect of TGFβ1 in Adipocyte on Inflammatory and Fibrotic Markers at Different Stages of Adipocyte Differentiation |
| title_short | The Effect of TGFβ1 in Adipocyte on Inflammatory and Fibrotic Markers at Different Stages of Adipocyte Differentiation |
| title_sort | effect of tgfβ1 in adipocyte on inflammatory and fibrotic markers at different stages of adipocyte differentiation |
| topic | TGFβ adipocyte stages of differentiation inflammation fibrosis |
| url | https://www.mdpi.com/1873-149X/29/4/50 |
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