Regulation of somatostatin expression by vitamin D3 and valproic acid in human adipose-derived mesenchymal stem cells
Abstract Background Adipose-derived mesenchymal stem cells (ADMSC) are non-haematopoietic, fibroblast-like multipotent progenitor cells. They have the potential for trilineage (adipocyte, chondrocyte and osteocyte) differentiation as well as differentiation into endocrine pancreatic progenitors. In...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-08-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13287-019-1330-x |
| _version_ | 1818684569967132672 |
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| author | Luise Doering Rahul Khatri Sebastian Friedrich Petry Heinrich Sauer Hans-Peter Howaldt Thomas Linn |
| author_facet | Luise Doering Rahul Khatri Sebastian Friedrich Petry Heinrich Sauer Hans-Peter Howaldt Thomas Linn |
| author_sort | Luise Doering |
| collection | DOAJ |
| description | Abstract Background Adipose-derived mesenchymal stem cells (ADMSC) are non-haematopoietic, fibroblast-like multipotent progenitor cells. They have the potential for trilineage (adipocyte, chondrocyte and osteocyte) differentiation as well as differentiation into endocrine pancreatic progenitors. In diabetic or cancer therapy, somatostatin (SST) expression plays a vital role. Small molecules such as valproic acid (VPA) and micronutrients like vitamin D3 have differentiation potential in ADMSC. Therefore, the aim of this study was to investigate the role of vitamin D3 machinery and its metabolic enzymes in ADMSC. Furthermore, the reprogramming effect of vitamin D3 and VPA was evaluated on somatostatin expression in pancreatic lineage differentiation. Methods ADMSC were characterised based on their cell surface marker profile using flow cytometry. Specific adipogenic and osteogenic differentiation protocols were used in this study. Gene expression of several pluripotent, endodermal, pancreatic progenitor and pancreatic endocrine lineage markers were investigated in native ADMSC and after stimulation with different concentration of vitamin D3 for five consecutive days (0, 50, 100, 150 nM) and VPA (0.5, 1, 1.5, 2 mM) by real-time PCR. Furthermore, somatostatin expression was confirmed with ELISA and immunocytochemistry. Results In ADMSC, the expression of somatostatin mRNA, the vitamin D receptor (VDR) and its metabolising enzymes 1 α-Hydroxylase, 24-Hydroxylase and 25-Hydroxylase were detected. Upon stimulation with vitamin D3, nuclear translocation of vitamin D receptor (VDR) was observed. Interestingly, the presence of vitamin D3 reduced the transcription of the somatostatin gene. By contrast, VPA treatment of cultivated ADMSC showed enhancing effect on somatostatin gene expression. No other pluripotent, endodermal, pancreatic progenitor or pancreatic endocrine lineage mRNA expression was modulated under the influence of vitamin D3 and VPA. Conclusion Human ADMSC carry the VDR. The vitamin D metabolising enzyme 25-Hydroxylase responded to the addition of vitamin D3. Moreover, our results demonstrate that somatostatin expression in ADMSC is constitutive, partially secreted and regulated by vitamin D3 and VPA. |
| first_indexed | 2024-12-17T10:52:44Z |
| format | Article |
| id | doaj.art-b78d466afa7d402c9cfe160835d4d635 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-17T10:52:44Z |
| publishDate | 2019-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-b78d466afa7d402c9cfe160835d4d6352022-12-21T21:51:56ZengBMCStem Cell Research & Therapy1757-65122019-08-0110111110.1186/s13287-019-1330-xRegulation of somatostatin expression by vitamin D3 and valproic acid in human adipose-derived mesenchymal stem cellsLuise Doering0Rahul Khatri1Sebastian Friedrich Petry2Heinrich Sauer3Hans-Peter Howaldt4Thomas Linn5Clinical Research Unit, Centre of Internal Medicine, Justus Liebig UniversityClinical Research Unit, Centre of Internal Medicine, Justus Liebig UniversityClinical Research Unit, Centre of Internal Medicine, Justus Liebig UniversityInstitute of Physiology, Justus Liebig UniversityDepartment of Oral and Maxillofacial Surgery, University Hospital of Giessen and MarburgClinical Research Unit, Centre of Internal Medicine, Justus Liebig UniversityAbstract Background Adipose-derived mesenchymal stem cells (ADMSC) are non-haematopoietic, fibroblast-like multipotent progenitor cells. They have the potential for trilineage (adipocyte, chondrocyte and osteocyte) differentiation as well as differentiation into endocrine pancreatic progenitors. In diabetic or cancer therapy, somatostatin (SST) expression plays a vital role. Small molecules such as valproic acid (VPA) and micronutrients like vitamin D3 have differentiation potential in ADMSC. Therefore, the aim of this study was to investigate the role of vitamin D3 machinery and its metabolic enzymes in ADMSC. Furthermore, the reprogramming effect of vitamin D3 and VPA was evaluated on somatostatin expression in pancreatic lineage differentiation. Methods ADMSC were characterised based on their cell surface marker profile using flow cytometry. Specific adipogenic and osteogenic differentiation protocols were used in this study. Gene expression of several pluripotent, endodermal, pancreatic progenitor and pancreatic endocrine lineage markers were investigated in native ADMSC and after stimulation with different concentration of vitamin D3 for five consecutive days (0, 50, 100, 150 nM) and VPA (0.5, 1, 1.5, 2 mM) by real-time PCR. Furthermore, somatostatin expression was confirmed with ELISA and immunocytochemistry. Results In ADMSC, the expression of somatostatin mRNA, the vitamin D receptor (VDR) and its metabolising enzymes 1 α-Hydroxylase, 24-Hydroxylase and 25-Hydroxylase were detected. Upon stimulation with vitamin D3, nuclear translocation of vitamin D receptor (VDR) was observed. Interestingly, the presence of vitamin D3 reduced the transcription of the somatostatin gene. By contrast, VPA treatment of cultivated ADMSC showed enhancing effect on somatostatin gene expression. No other pluripotent, endodermal, pancreatic progenitor or pancreatic endocrine lineage mRNA expression was modulated under the influence of vitamin D3 and VPA. Conclusion Human ADMSC carry the VDR. The vitamin D metabolising enzyme 25-Hydroxylase responded to the addition of vitamin D3. Moreover, our results demonstrate that somatostatin expression in ADMSC is constitutive, partially secreted and regulated by vitamin D3 and VPA.http://link.springer.com/article/10.1186/s13287-019-1330-xHuman adipose-derived mesenchymal stem cellsSomatostatin expression |
| spellingShingle | Luise Doering Rahul Khatri Sebastian Friedrich Petry Heinrich Sauer Hans-Peter Howaldt Thomas Linn Regulation of somatostatin expression by vitamin D3 and valproic acid in human adipose-derived mesenchymal stem cells Stem Cell Research & Therapy Human adipose-derived mesenchymal stem cells Somatostatin expression |
| title | Regulation of somatostatin expression by vitamin D3 and valproic acid in human adipose-derived mesenchymal stem cells |
| title_full | Regulation of somatostatin expression by vitamin D3 and valproic acid in human adipose-derived mesenchymal stem cells |
| title_fullStr | Regulation of somatostatin expression by vitamin D3 and valproic acid in human adipose-derived mesenchymal stem cells |
| title_full_unstemmed | Regulation of somatostatin expression by vitamin D3 and valproic acid in human adipose-derived mesenchymal stem cells |
| title_short | Regulation of somatostatin expression by vitamin D3 and valproic acid in human adipose-derived mesenchymal stem cells |
| title_sort | regulation of somatostatin expression by vitamin d3 and valproic acid in human adipose derived mesenchymal stem cells |
| topic | Human adipose-derived mesenchymal stem cells Somatostatin expression |
| url | http://link.springer.com/article/10.1186/s13287-019-1330-x |
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