PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
Low Dose Rate Radiation Induced Secretion of TGF-β3 Together With an Activator in Small Extracellular Vesicles Modifies Low Dose Hyper-Radiosensitivity Through ALK1 Binding
Version 1
: Received: 11 July 2022 / Approved: 12 July 2022 / Online: 12 July 2022 (09:25:07 CEST)
How to cite:
Hanson, I.; Pitman, K.E.; Altanerova, U.; Altaner, Č.; Malinen, E.; Edin, N.F.J. Low Dose Rate Radiation Induced Secretion of TGF-β3 Together With an Activator in Small Extracellular Vesicles Modifies Low Dose Hyper-Radiosensitivity Through ALK1 Binding. Preprints2022, 2022070182. https://doi.org/10.20944/preprints202207.0182.v1
Hanson, I.; Pitman, K.E.; Altanerova, U.; Altaner, Č.; Malinen, E.; Edin, N.F.J. Low Dose Rate Radiation Induced Secretion of TGF-β3 Together With an Activator in Small Extracellular Vesicles Modifies Low Dose Hyper-Radiosensitivity Through ALK1 Binding. Preprints 2022, 2022070182. https://doi.org/10.20944/preprints202207.0182.v1
Hanson, I.; Pitman, K.E.; Altanerova, U.; Altaner, Č.; Malinen, E.; Edin, N.F.J. Low Dose Rate Radiation Induced Secretion of TGF-β3 Together With an Activator in Small Extracellular Vesicles Modifies Low Dose Hyper-Radiosensitivity Through ALK1 Binding. Preprints2022, 2022070182. https://doi.org/10.20944/preprints202207.0182.v1
APA Style
Hanson, I., Pitman, K.E., Altanerova, U., Altaner, Č., Malinen, E., & Edin, N.F.J. (2022). Low Dose Rate Radiation Induced Secretion of TGF-β3 Together With an Activator in Small Extracellular Vesicles Modifies Low Dose Hyper-Radiosensitivity Through ALK1 Binding. Preprints. https://doi.org/10.20944/preprints202207.0182.v1
Chicago/Turabian Style
Hanson, I., Eirik Malinen and Nina Frederike Jeppesen Edin. 2022 "Low Dose Rate Radiation Induced Secretion of TGF-β3 Together With an Activator in Small Extracellular Vesicles Modifies Low Dose Hyper-Radiosensitivity Through ALK1 Binding" Preprints. https://doi.org/10.20944/preprints202207.0182.v1
Abstract
Hyper-radiosensitivity (HRS) is the increased sensitivity to low doses of ionizing radiation observed in most cell lines. We previously demonstrated that HRS is permanently abolished in cells irradiated at a low dose rate (LDR), in a mechanism dependent on transforming growth factor β3 (TGF-β3). In this study, we aimed to elucidate the activation and receptor binding of TGF-β3 in this mechanism. T-47D cells were pre-treated with inhibitors of potential receptors and activators of TGF-β3, along with addition of small extracellular vesicles (sEVs) from LDR primed cells, before their radiosensitivity was assessed by the clonogenic assay. The protein content of sEVs from LDR primed cells was analyzed with mass spectrometry. Our results show that sEVs contain TGF-β3 regardless of priming status, but only sEVs from LDR primed cells remove HRS in reporter cells. Inhibition of the matrix metalloproteinase (MMP) family prevents removal of HRS, suggesting an MMP-dependent activation of TGF-β3 in the LDR primed cells. We demonstrate a functional interaction between TGF-β3 and activin receptor like kinase 1 (ALK1), by showing that TGF-β3 removes HRS through ALK1 binding, independent of ALK5 and TGF-βRII. These results are an important contribution to a more comprehensive understanding of the mechanism behind TGF-β3 mediated removal of HRS.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
,
,
,
,
,
