Mesenchymal stem cell (MSC)-mediated survival of insulin producing pancreatic β-cells during cellular stress involves signalling via Akt and ERK1/2
| Autor: | Leonie Lang, Weiwei Zhang, Christina Jäger, M Alt, Peter J. Feilen, Günter Päth, Chune Liu, Nikolaos Perakakis, Jochen Seufert, Katharina Laubner, J Straetener, Natia Peradze |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cell Survival MAP Kinase Signaling System Interleukin-1beta Biochemistry Streptozocin Cell therapy 03 medical and health sciences 0302 clinical medicine Endocrinology Downregulation and upregulation Cell Movement Stress Physiological Insulin-Secreting Cells Alloxan medicine Animals Humans Insulin Phosphorylation Rats Wistar Molecular Biology Protein kinase B Telomerase Caspase 7 Chemistry Caspase 3 Pancreatic islets Mesenchymal stem cell NF-kappa B Mesenchymal Stem Cells NFKB1 Streptozotocin Cytoprotection Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Poly(ADP-ribose) Polymerases Proto-Oncogene Proteins c-akt medicine.drug |
| Zdroj: | Molecular and cellular endocrinology. 473 |
| ISSN: | 1872-8057 |
| Popis: | Mesenchymal stem cells (MSC) are of interest for cell therapy since their secreted factors mediate immunomodulation and support tissue regeneration. This study investigated the direct humoral interactions between MSC and pancreatic β-cells using human telomerase-immortalized MSC (hMSC-TERT) and rat insulinoma-derived INS-1E β-cells. hMSC-TERT supported survival of cocultured INS-1E β-cells during cellular stress by alloxan (ALX) and streptozotocin (STZ), but not in response to IL-1β. Accordingly, hMSC-TERT had no effect on inflammatory cytokine-related signalling via NF-kB and p-JNK but maintained p-Akt and upregulated p-ERK1/2. Inhibition of either p-Akt or p-ERK1/2 did not abolish protection by hMSC-TERT but activated the respective non-inhibited pathway. This suggests that one pathway compensates for the other. Main results were confirmed in mouse islets except hMSC-TERT-mediated upregulation of p-ERK1/2. Therefore, MSC promote β-cell survival by preservation of p-Akt signalling and further involve p-ERK1/2 activation in certain conditions such as loss of p-Akt or insulinoma background. |
| Databáze: | OpenAIRE |
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