Cyclic hypoxia conditioning alters the content of myoblast-derived extracellular vesicles and enhances their cell-protective functions

Yan Yan; Tingting Gu; Stine Duelund Kaas Christensen; Junyi Su; Thomas Ravn Lassen; Marie Vognstoft Hjortbak; Iju Lo; Susanne Trillingsgaard Venø; Andrea Erzsebet Tóth; Ping Song; Morten Schallburg Nielsen; Hans Erik Bøtker; Blagoy Blagoev; Kim Ryun Drasbek; Jørgen Kjems

doi:10.3390/biomedicines9091211

Cyclic hypoxia conditioning alters the content of myoblast-derived extracellular vesicles and enhances their cell-protective functions

Yan Yan, Tingting Gu, Stine Duelund Kaas Christensen, Junyi Su, Thomas Ravn Lassen, Marie Vognstoft Hjortbak, Iju Lo, Susanne Trillingsgaard Venø, Andrea Erzsebet Tóth, Ping Song, Morten Schallburg Nielsen, Hans Erik Bøtker, Blagoy Blagoev, Kim Ryun Drasbek, Jørgen Kjems^*

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

8 Citations (Scopus)

Abstract

Remote ischemic conditioning (RIC) is a procedure that can attenuate ischemic-reperfusion injury by conducting brief cycles of ischemia and reperfusion in the arm or leg. Extracellular vesicles (EVs) circulating in the bloodstream can release their content into recipient cells to confer protective function on ischemia-reperfusion injured (IRI) organs. Skeletal muscle cells are potential candidates to release EVs as a protective signal during RIC. In this study, we used C2C12 cells as a model system and performed cyclic hypoxia-reoxygenation (HR) to mimic RIC. EVs were collected and subjected to small RNA profiling and proteomics. HR induced a distinct shift in the miRNA profile and protein content in EVs. HR EV treatment restored cell viability, dampened inflammation, and enhanced tube formation in in vitro assays. In vivo, HR EVs showed increased accumulation in the ischemic brain compared to EVs secreted from normoxic culture (N EVs) in a mouse undergoing transient middle cerebral artery occlusion (tMCAO). We conclude that HR conditioning changes the miRNA and protein profile in EVs released by C2C12 cells and enhances the protective signal in the EVs to recipient cells in vitro.

Original language	English
Article number	1211
Journal	Biomedicines
Volume	9
Issue	9
Number of pages	20
ISSN	2227-9059
DOIs	https://doi.org/10.3390/biomedicines9091211
Publication status	Published - Sept 2021

Keywords

Cyclic hypoxia-reoxygenation
Extracellular vesicles
MicroRNAs
Myoblast
Proteins
Remote ischemic conditioning

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Yan, Y., Gu, T., Christensen, S. D. K., Su, J., Lassen, T. R., Hjortbak, M. V., Lo, I., Venø, S. T., Tóth, A. E., Song, P., Nielsen, M. S., Bøtker, H. E., Blagoev, B., Drasbek, K. R., & Kjems, J. (2021). Cyclic hypoxia conditioning alters the content of myoblast-derived extracellular vesicles and enhances their cell-protective functions. Biomedicines, 9(9), Article 1211. https://doi.org/10.3390/biomedicines9091211

@article{02654b23fd104b748d3fa31a769b1962,

title = "Cyclic hypoxia conditioning alters the content of myoblast-derived extracellular vesicles and enhances their cell-protective functions",

abstract = "Remote ischemic conditioning (RIC) is a procedure that can attenuate ischemic-reperfusion injury by conducting brief cycles of ischemia and reperfusion in the arm or leg. Extracellular vesicles (EVs) circulating in the bloodstream can release their content into recipient cells to confer protective function on ischemia-reperfusion injured (IRI) organs. Skeletal muscle cells are potential candidates to release EVs as a protective signal during RIC. In this study, we used C2C12 cells as a model system and performed cyclic hypoxia-reoxygenation (HR) to mimic RIC. EVs were collected and subjected to small RNA profiling and proteomics. HR induced a distinct shift in the miRNA profile and protein content in EVs. HR EV treatment restored cell viability, dampened inflammation, and enhanced tube formation in in vitro assays. In vivo, HR EVs showed increased accumulation in the ischemic brain compared to EVs secreted from normoxic culture (N EVs) in a mouse undergoing transient middle cerebral artery occlusion (tMCAO). We conclude that HR conditioning changes the miRNA and protein profile in EVs released by C2C12 cells and enhances the protective signal in the EVs to recipient cells in vitro.",

keywords = "Cyclic hypoxia-reoxygenation, Extracellular vesicles, MicroRNAs, Myoblast, Proteins, Remote ischemic conditioning",

author = "Yan Yan and Tingting Gu and Christensen, {Stine Duelund Kaas} and Junyi Su and Lassen, {Thomas Ravn} and Hjortbak, {Marie Vognstoft} and Iju Lo and Ven{\o}, {Susanne Trillingsgaard} and T{\'o}th, {Andrea Erzsebet} and Ping Song and Nielsen, {Morten Schallburg} and B{\o}tker, {Hans Erik} and Blagoy Blagoev and Drasbek, {Kim Ryun} and J{\o}rgen Kjems",

note = "Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = sep,

doi = "10.3390/biomedicines9091211",

language = "English",

volume = "9",

journal = "Biomedicines",

issn = "2227-9059",

publisher = "MDPI",

number = "9",

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Yan, Y, Gu, T, Christensen, SDK, Su, J, Lassen, TR, Hjortbak, MV, Lo, I, Venø, ST, Tóth, AE, Song, P , Nielsen, MS , Bøtker, HE, Blagoev, B, Drasbek, KR & Kjems, J 2021, 'Cyclic hypoxia conditioning alters the content of myoblast-derived extracellular vesicles and enhances their cell-protective functions', Biomedicines, vol. 9, no. 9, 1211. https://doi.org/10.3390/biomedicines9091211

Cyclic hypoxia conditioning alters the content of myoblast-derived extracellular vesicles and enhances their cell-protective functions. / Yan, Yan; Gu, Tingting; Christensen, Stine Duelund Kaas et al.
In: Biomedicines, Vol. 9, No. 9, 1211, 09.2021.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Cyclic hypoxia conditioning alters the content of myoblast-derived extracellular vesicles and enhances their cell-protective functions

AU - Yan, Yan

AU - Gu, Tingting

AU - Christensen, Stine Duelund Kaas

AU - Su, Junyi

AU - Lassen, Thomas Ravn

AU - Hjortbak, Marie Vognstoft

AU - Lo, Iju

AU - Venø, Susanne Trillingsgaard

AU - Tóth, Andrea Erzsebet

AU - Song, Ping

AU - Nielsen, Morten Schallburg

AU - Bøtker, Hans Erik

AU - Blagoev, Blagoy

AU - Drasbek, Kim Ryun

AU - Kjems, Jørgen

PY - 2021/9

Y1 - 2021/9

N2 - Remote ischemic conditioning (RIC) is a procedure that can attenuate ischemic-reperfusion injury by conducting brief cycles of ischemia and reperfusion in the arm or leg. Extracellular vesicles (EVs) circulating in the bloodstream can release their content into recipient cells to confer protective function on ischemia-reperfusion injured (IRI) organs. Skeletal muscle cells are potential candidates to release EVs as a protective signal during RIC. In this study, we used C2C12 cells as a model system and performed cyclic hypoxia-reoxygenation (HR) to mimic RIC. EVs were collected and subjected to small RNA profiling and proteomics. HR induced a distinct shift in the miRNA profile and protein content in EVs. HR EV treatment restored cell viability, dampened inflammation, and enhanced tube formation in in vitro assays. In vivo, HR EVs showed increased accumulation in the ischemic brain compared to EVs secreted from normoxic culture (N EVs) in a mouse undergoing transient middle cerebral artery occlusion (tMCAO). We conclude that HR conditioning changes the miRNA and protein profile in EVs released by C2C12 cells and enhances the protective signal in the EVs to recipient cells in vitro.

AB - Remote ischemic conditioning (RIC) is a procedure that can attenuate ischemic-reperfusion injury by conducting brief cycles of ischemia and reperfusion in the arm or leg. Extracellular vesicles (EVs) circulating in the bloodstream can release their content into recipient cells to confer protective function on ischemia-reperfusion injured (IRI) organs. Skeletal muscle cells are potential candidates to release EVs as a protective signal during RIC. In this study, we used C2C12 cells as a model system and performed cyclic hypoxia-reoxygenation (HR) to mimic RIC. EVs were collected and subjected to small RNA profiling and proteomics. HR induced a distinct shift in the miRNA profile and protein content in EVs. HR EV treatment restored cell viability, dampened inflammation, and enhanced tube formation in in vitro assays. In vivo, HR EVs showed increased accumulation in the ischemic brain compared to EVs secreted from normoxic culture (N EVs) in a mouse undergoing transient middle cerebral artery occlusion (tMCAO). We conclude that HR conditioning changes the miRNA and protein profile in EVs released by C2C12 cells and enhances the protective signal in the EVs to recipient cells in vitro.

KW - Cyclic hypoxia-reoxygenation

KW - Extracellular vesicles

KW - MicroRNAs

KW - Myoblast

KW - Proteins

KW - Remote ischemic conditioning

UR - http://www.scopus.com/inward/record.url?scp=85115239302&partnerID=8YFLogxK

U2 - 10.3390/biomedicines9091211

DO - 10.3390/biomedicines9091211

M3 - Journal article

C2 - 34572398

AN - SCOPUS:85115239302

SN - 2227-9059

VL - 9

JO - Biomedicines

JF - Biomedicines

IS - 9

M1 - 1211

ER -

Cyclic hypoxia conditioning alters the content of myoblast-derived extracellular vesicles and enhances their cell-protective functions

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Keywords

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