Transcription Factors STAT3 and MYC Are Key Players of Human Platelet Lysate-Induced Cell Proliferation
Human platelet lysate (HPL) is an efficient alternative for animal serum supplements, significantly enhancing stromal cell proliferation. However, the molecular mechanism behind this growth-promoting effect remains elusive. The aim of this study was to investigate the effect of HPL on cell cycle gen...
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| Format: | Article |
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/24/15782 |
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| author | Michaela Oeller Heidi Jaksch-Bogensperger Markus Templin Renate Gehwolf Eva Rohde Katharina Schallmoser Sandra Laner-Plamberger |
| author_facet | Michaela Oeller Heidi Jaksch-Bogensperger Markus Templin Renate Gehwolf Eva Rohde Katharina Schallmoser Sandra Laner-Plamberger |
| author_sort | Michaela Oeller |
| collection | DOAJ |
| description | Human platelet lysate (HPL) is an efficient alternative for animal serum supplements, significantly enhancing stromal cell proliferation. However, the molecular mechanism behind this growth-promoting effect remains elusive. The aim of this study was to investigate the effect of HPL on cell cycle gene expression in different human stromal cells and to identify the main key players that mediate HPL’s growth-enhancing effect. RT-qPCR and an antibody array revealed significant upregulation of cell cycle genes in stromal cells cultured in HPL. As HPL is rich in growth factors that are ligands of tyrosine kinase receptor (TKR) pathways, we used TKR inhibitors and could significantly reduce cell proliferation. Genome profiling, RT-qPCR and Western blotting revealed an enhanced expression of the transcription factors signal transducer and activator of transcription 3 (STAT3) and MYC, both known TKR downstream effectors and stimulators of cell proliferation, in response to HPL. In addition, specifically blocking STAT3 resulted in reduced cell proliferation and expression of cell cycle genes. Our data indicate that HPL-enhanced cell proliferation can, at least in part, be explained by the TKR-enhanced expression of STAT3 and MYC, which in turn induce the expression of genes being involved in the promotion and control of the cell cycle. |
| first_indexed | 2024-03-09T16:20:06Z |
| format | Article |
| id | doaj.art-d5715d3f9c6c45c797053af2be7fc877 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:20:06Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d5715d3f9c6c45c797053af2be7fc8772023-11-24T15:27:52ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123241578210.3390/ijms232415782Transcription Factors STAT3 and MYC Are Key Players of Human Platelet Lysate-Induced Cell ProliferationMichaela Oeller0Heidi Jaksch-Bogensperger1Markus Templin2Renate Gehwolf3Eva Rohde4Katharina Schallmoser5Sandra Laner-Plamberger6Department of Transfusion Medicine, Salzburger Landeskliniken (SALK) & Paracelsus Medical University Salzburg (PMU), 5020 Salzburg, AustriaDepartment of Obstetrics and Gynaecology, Salzburger Landeskliniken (SALK) & Paracelsus Medical University Salzburg (PMU), 5020 Salzburg, AustriaNMI Natural and Medical Sciences Institute at the University of Tuebingen, 72770 Reutlingen, GermanySpinal Cord Injury and Tissue Regeneration Center Salzburg, PMU Salzburg, 5020 Salzburg, AustriaDepartment of Transfusion Medicine, Salzburger Landeskliniken (SALK) & Paracelsus Medical University Salzburg (PMU), 5020 Salzburg, AustriaDepartment of Transfusion Medicine, Salzburger Landeskliniken (SALK) & Paracelsus Medical University Salzburg (PMU), 5020 Salzburg, AustriaDepartment of Transfusion Medicine, Salzburger Landeskliniken (SALK) & Paracelsus Medical University Salzburg (PMU), 5020 Salzburg, AustriaHuman platelet lysate (HPL) is an efficient alternative for animal serum supplements, significantly enhancing stromal cell proliferation. However, the molecular mechanism behind this growth-promoting effect remains elusive. The aim of this study was to investigate the effect of HPL on cell cycle gene expression in different human stromal cells and to identify the main key players that mediate HPL’s growth-enhancing effect. RT-qPCR and an antibody array revealed significant upregulation of cell cycle genes in stromal cells cultured in HPL. As HPL is rich in growth factors that are ligands of tyrosine kinase receptor (TKR) pathways, we used TKR inhibitors and could significantly reduce cell proliferation. Genome profiling, RT-qPCR and Western blotting revealed an enhanced expression of the transcription factors signal transducer and activator of transcription 3 (STAT3) and MYC, both known TKR downstream effectors and stimulators of cell proliferation, in response to HPL. In addition, specifically blocking STAT3 resulted in reduced cell proliferation and expression of cell cycle genes. Our data indicate that HPL-enhanced cell proliferation can, at least in part, be explained by the TKR-enhanced expression of STAT3 and MYC, which in turn induce the expression of genes being involved in the promotion and control of the cell cycle.https://www.mdpi.com/1422-0067/23/24/15782human platelet lysate (HPL)signal transducer and activator of transcription 3 (STAT3)MYChuman mesenchymal stromal cells (MSCs)proliferation |
| spellingShingle | Michaela Oeller Heidi Jaksch-Bogensperger Markus Templin Renate Gehwolf Eva Rohde Katharina Schallmoser Sandra Laner-Plamberger Transcription Factors STAT3 and MYC Are Key Players of Human Platelet Lysate-Induced Cell Proliferation International Journal of Molecular Sciences human platelet lysate (HPL) signal transducer and activator of transcription 3 (STAT3) MYC human mesenchymal stromal cells (MSCs) proliferation |
| title | Transcription Factors STAT3 and MYC Are Key Players of Human Platelet Lysate-Induced Cell Proliferation |
| title_full | Transcription Factors STAT3 and MYC Are Key Players of Human Platelet Lysate-Induced Cell Proliferation |
| title_fullStr | Transcription Factors STAT3 and MYC Are Key Players of Human Platelet Lysate-Induced Cell Proliferation |
| title_full_unstemmed | Transcription Factors STAT3 and MYC Are Key Players of Human Platelet Lysate-Induced Cell Proliferation |
| title_short | Transcription Factors STAT3 and MYC Are Key Players of Human Platelet Lysate-Induced Cell Proliferation |
| title_sort | transcription factors stat3 and myc are key players of human platelet lysate induced cell proliferation |
| topic | human platelet lysate (HPL) signal transducer and activator of transcription 3 (STAT3) MYC human mesenchymal stromal cells (MSCs) proliferation |
| url | https://www.mdpi.com/1422-0067/23/24/15782 |
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