The production of fibroblast growth factor 23 is controlled by TGF-β2
Abstract Transforming growth factor-β (TGF-β) is a cytokine produced by many cell types and implicated in cell growth, differentiation, apoptosis, and inflammation. It stimulates store-operated calcium entry (SOCE) through the calcium release-activated calcium (CRAC) channel Orai1/Stim1 in endometri...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-05226-y |
| _version_ | 1830207117864206336 |
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| author | Martina Feger Philipp Hase Bingbing Zhang Frank Hirche Philipp Glosse Florian Lang Michael Föller |
| author_facet | Martina Feger Philipp Hase Bingbing Zhang Frank Hirche Philipp Glosse Florian Lang Michael Föller |
| author_sort | Martina Feger |
| collection | DOAJ |
| description | Abstract Transforming growth factor-β (TGF-β) is a cytokine produced by many cell types and implicated in cell growth, differentiation, apoptosis, and inflammation. It stimulates store-operated calcium entry (SOCE) through the calcium release-activated calcium (CRAC) channel Orai1/Stim1 in endometrial Ishikawa cells. Bone cells generate fibroblast growth factor (FGF) 23, which inhibits renal phosphate reabsorption and 1,25(OH)2D3 formation in concert with its co-receptor Klotho. Moreover, Klotho and FGF23 counteract aging and age-related clinical conditions. FGF23 production is dependent on Orai1-mediated SOCE and inflammation. Here, we explored a putative role of TGF-β2 in FGF23 synthesis. To this end, UMR106 osteoblast-like cells were cultured, Fgf23 transcript levels determined by qRT-PCR, FGF23 protein measured by ELISA, and SOCE analyzed by fluorescence optics. UMR106 cells expressed TGF-β receptors 1 and 2. TGF-β2 enhanced SOCE and potently stimulated the production of FGF23, an effect significantly attenuated by SB431542, an inhibitor of the transforming growth factor-β (TGF-β) type I receptor activin receptor-like kinases ALK5, ALK4, and ALK7. Furthermore, the TGF-β2 effect on FGF23 production was blunted by SOCE inhibitor 2-APB. We conclude that TGF-β2 induces FGF23 production, an effect involving up-regulation of SOCE. |
| first_indexed | 2024-12-18T04:25:38Z |
| format | Article |
| id | doaj.art-fefce797720346d5b0acfe927ed1297b |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T04:25:38Z |
| publishDate | 2017-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-fefce797720346d5b0acfe927ed1297b2022-12-21T21:21:07ZengNature PortfolioScientific Reports2045-23222017-07-01711710.1038/s41598-017-05226-yThe production of fibroblast growth factor 23 is controlled by TGF-β2Martina Feger0Philipp Hase1Bingbing Zhang2Frank Hirche3Philipp Glosse4Florian Lang5Michael Föller6Institute of Agricultural and Nutritional Sciences, Martin-Luther University Halle-WittenbergInstitute of Agricultural and Nutritional Sciences, Martin-Luther University Halle-WittenbergDepartment of Physiology, Eberhard-Karls University of TübingenInstitute of Agricultural and Nutritional Sciences, Martin-Luther University Halle-WittenbergInstitute of Agricultural and Nutritional Sciences, Martin-Luther University Halle-WittenbergDepartment of Physiology, Eberhard-Karls University of TübingenInstitute of Agricultural and Nutritional Sciences, Martin-Luther University Halle-WittenbergAbstract Transforming growth factor-β (TGF-β) is a cytokine produced by many cell types and implicated in cell growth, differentiation, apoptosis, and inflammation. It stimulates store-operated calcium entry (SOCE) through the calcium release-activated calcium (CRAC) channel Orai1/Stim1 in endometrial Ishikawa cells. Bone cells generate fibroblast growth factor (FGF) 23, which inhibits renal phosphate reabsorption and 1,25(OH)2D3 formation in concert with its co-receptor Klotho. Moreover, Klotho and FGF23 counteract aging and age-related clinical conditions. FGF23 production is dependent on Orai1-mediated SOCE and inflammation. Here, we explored a putative role of TGF-β2 in FGF23 synthesis. To this end, UMR106 osteoblast-like cells were cultured, Fgf23 transcript levels determined by qRT-PCR, FGF23 protein measured by ELISA, and SOCE analyzed by fluorescence optics. UMR106 cells expressed TGF-β receptors 1 and 2. TGF-β2 enhanced SOCE and potently stimulated the production of FGF23, an effect significantly attenuated by SB431542, an inhibitor of the transforming growth factor-β (TGF-β) type I receptor activin receptor-like kinases ALK5, ALK4, and ALK7. Furthermore, the TGF-β2 effect on FGF23 production was blunted by SOCE inhibitor 2-APB. We conclude that TGF-β2 induces FGF23 production, an effect involving up-regulation of SOCE.https://doi.org/10.1038/s41598-017-05226-y |
| spellingShingle | Martina Feger Philipp Hase Bingbing Zhang Frank Hirche Philipp Glosse Florian Lang Michael Föller The production of fibroblast growth factor 23 is controlled by TGF-β2 Scientific Reports |
| title | The production of fibroblast growth factor 23 is controlled by TGF-β2 |
| title_full | The production of fibroblast growth factor 23 is controlled by TGF-β2 |
| title_fullStr | The production of fibroblast growth factor 23 is controlled by TGF-β2 |
| title_full_unstemmed | The production of fibroblast growth factor 23 is controlled by TGF-β2 |
| title_short | The production of fibroblast growth factor 23 is controlled by TGF-β2 |
| title_sort | production of fibroblast growth factor 23 is controlled by tgf β2 |
| url | https://doi.org/10.1038/s41598-017-05226-y |
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