Promotion of beta cell proliferation through DYRK kinase inhibition using the marine natural product breitfussin C
Abstract Pro-inflammatory cytokines, like interleukin-1 beta and interferon gamma, are known to activate signalling pathways causing pancreatic beta cell death and dysfunction, contributing to the onset of diabetes. Targeting cytokine signalling pathways offers a potential strategy to slow or even h...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-85178-w |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841544785649729536 |
|---|---|
| author | Sara Ullsten Kine Østnes Hansen Guillaume Axel Petit Espen Holst Hansen Jeanette Hammer Andersen |
| author_facet | Sara Ullsten Kine Østnes Hansen Guillaume Axel Petit Espen Holst Hansen Jeanette Hammer Andersen |
| author_sort | Sara Ullsten |
| collection | DOAJ |
| description | Abstract Pro-inflammatory cytokines, like interleukin-1 beta and interferon gamma, are known to activate signalling pathways causing pancreatic beta cell death and dysfunction, contributing to the onset of diabetes. Targeting cytokine signalling pathways offers a potential strategy to slow or even halt disease progression, reducing reliance on exogenous insulin and improving glucose regulation. This study explores the protective and proliferative effects of breitfussin C (BfC), a natural compound isolated from the Arctic marine hydrozoan Thuiaria breitfussi, on pancreatic beta cells exposed to pro-inflammatory cytokines. Using the beta cell line RIN-M5F, we assessed the protective effects of BfC through a MTS assay for cell viability, caspase 3/7 activity for apoptosis, and EdU incorporation and cell cycle distribution for proliferation. Additionally, we investigated BfC’s inhibitory effects on the DYRK family of kinases using kinase activity and binding assays, western blotting, and docking simulations. Our findings reveal that BfC treatment effectively increases beta cell proliferation and counteracts cytokine-induced decrease in proliferation. The proliferative effect is associated with inhibition of DYRK kinases and a subsequent decrease in the cell cycle inhibitor p27KIP. These results suggest that BfC mediates beta cell-protective effect by promoting proliferation through DYRK inhibition, highlighting its potential as a molecular starting point for the development of a therapeutic agent against diabetes. |
| format | Article |
| id | doaj-art-e60c953716cb4a6c9d942fc97ec5158c |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-e60c953716cb4a6c9d942fc97ec5158c2025-01-12T12:17:12ZengNature PortfolioScientific Reports2045-23222025-01-011511810.1038/s41598-025-85178-wPromotion of beta cell proliferation through DYRK kinase inhibition using the marine natural product breitfussin CSara Ullsten0Kine Østnes Hansen1Guillaume Axel Petit2Espen Holst Hansen3Jeanette Hammer Andersen4MARBIO, UiT – The Arctic University of NorwayMARBIO, UiT – The Arctic University of NorwayMARBIO, UiT – The Arctic University of NorwayMARBIO, UiT – The Arctic University of NorwayMARBIO, UiT – The Arctic University of NorwayAbstract Pro-inflammatory cytokines, like interleukin-1 beta and interferon gamma, are known to activate signalling pathways causing pancreatic beta cell death and dysfunction, contributing to the onset of diabetes. Targeting cytokine signalling pathways offers a potential strategy to slow or even halt disease progression, reducing reliance on exogenous insulin and improving glucose regulation. This study explores the protective and proliferative effects of breitfussin C (BfC), a natural compound isolated from the Arctic marine hydrozoan Thuiaria breitfussi, on pancreatic beta cells exposed to pro-inflammatory cytokines. Using the beta cell line RIN-M5F, we assessed the protective effects of BfC through a MTS assay for cell viability, caspase 3/7 activity for apoptosis, and EdU incorporation and cell cycle distribution for proliferation. Additionally, we investigated BfC’s inhibitory effects on the DYRK family of kinases using kinase activity and binding assays, western blotting, and docking simulations. Our findings reveal that BfC treatment effectively increases beta cell proliferation and counteracts cytokine-induced decrease in proliferation. The proliferative effect is associated with inhibition of DYRK kinases and a subsequent decrease in the cell cycle inhibitor p27KIP. These results suggest that BfC mediates beta cell-protective effect by promoting proliferation through DYRK inhibition, highlighting its potential as a molecular starting point for the development of a therapeutic agent against diabetes.https://doi.org/10.1038/s41598-025-85178-wDiabetesBeta cellsProliferationKinase inhibitionDYRKCytokines |
| spellingShingle | Sara Ullsten Kine Østnes Hansen Guillaume Axel Petit Espen Holst Hansen Jeanette Hammer Andersen Promotion of beta cell proliferation through DYRK kinase inhibition using the marine natural product breitfussin C Scientific Reports Diabetes Beta cells Proliferation Kinase inhibition DYRK Cytokines |
| title | Promotion of beta cell proliferation through DYRK kinase inhibition using the marine natural product breitfussin C |
| title_full | Promotion of beta cell proliferation through DYRK kinase inhibition using the marine natural product breitfussin C |
| title_fullStr | Promotion of beta cell proliferation through DYRK kinase inhibition using the marine natural product breitfussin C |
| title_full_unstemmed | Promotion of beta cell proliferation through DYRK kinase inhibition using the marine natural product breitfussin C |
| title_short | Promotion of beta cell proliferation through DYRK kinase inhibition using the marine natural product breitfussin C |
| title_sort | promotion of beta cell proliferation through dyrk kinase inhibition using the marine natural product breitfussin c |
| topic | Diabetes Beta cells Proliferation Kinase inhibition DYRK Cytokines |
| url | https://doi.org/10.1038/s41598-025-85178-w |
| work_keys_str_mv | AT saraullsten promotionofbetacellproliferationthroughdyrkkinaseinhibitionusingthemarinenaturalproductbreitfussinc AT kineøstneshansen promotionofbetacellproliferationthroughdyrkkinaseinhibitionusingthemarinenaturalproductbreitfussinc AT guillaumeaxelpetit promotionofbetacellproliferationthroughdyrkkinaseinhibitionusingthemarinenaturalproductbreitfussinc AT espenholsthansen promotionofbetacellproliferationthroughdyrkkinaseinhibitionusingthemarinenaturalproductbreitfussinc AT jeanettehammerandersen promotionofbetacellproliferationthroughdyrkkinaseinhibitionusingthemarinenaturalproductbreitfussinc |