Horizontal transfer of exosomal microRNAs transduce apoptotic signals between pancreatic beta-cells

Autor: Romano Regazzi, Claudiane Guay, Sophie Rome, Véronique Menoud
Přispěvatelé: Université de Lausanne (UNIL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Swiss National Science Foundation 310030-146138 European Foundation for the Study of Diabetes Fondation pour la Recherche Medicale DRM20101220456 biopharmaceutical company AstraZeneca Fonds de la Recherche en Sante du Quebec Societe Francophone du Diabete Canadian Diabetes Association, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Université de Lausanne = University of Lausanne (UNIL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pillet, Lauriane
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Apoptosis
[SDV]Life Sciences [q-bio]
Cell
030209 endocrinology & metabolism
Biology
Exosomes
MicroRNAs/*metabolism
Biochemistry
Cell Line
Mice
03 medical and health sciences
0302 clinical medicine
Insulin-Secreting Cells
microRNA
Caenorhabditis elegans/genetics/metabolism
medicine
Humans
Animals
Caenorhabditis elegans
Receptor
Molecular Biology
030304 developmental biology
0303 health sciences
MicroRNAs
Pancreatic beta-cells
Cell-to-cell communication
Diabetes
EXPRESSION CONTRIBUTE
REGULATORY FUNCTIONS
NONCODING RNAS
INS-1 CELLS
VESICLES
DYSFUNCTION
ISLETS
MICROVESICLES
SECRETION
COMPLEXES
Research
Metabolic disorder
Biological Transport
Insulin-Secreting Cells/*metabolism
Cell Biology
medicine.disease
Signal Transduction
Microvesicles
Rats
Cell biology
[SDV] Life Sciences [q-bio]
medicine.anatomical_structure
Cell culture
Exosomes/*metabolism
Signal transduction
Zdroj: Cell Communication and Signaling, vol. 13, pp. 17
Cell Communication and Signaling
Cell Communication and Signaling, BioMed Central, 2015, 13, pp.17. ⟨10.1186/s12964-015-0097-7⟩
Cell communication and signaling : CCS
Cell Communication and Signaling, 2015, 13, pp.17. ⟨10.1186/s12964-015-0097-7⟩
Cell Communication and Signaling : CCS
Cell Communication and Signaling (13), . (2015)
ISSN: 1478-811X
DOI: 10.1186/s12964-015-0097-7⟩
Popis: Background Diabetes mellitus is a common metabolic disorder characterized by dysfunction of insulin-secreting pancreatic beta-cells. MicroRNAs are important regulators of beta-cell activities. These non-coding RNAs have recently been discovered to exert their effects not only inside the cell producing them but, upon exosome-mediated transfer, also in other recipient cells. This novel communication mode remains unexplored in pancreatic beta-cells. In the present study, the microRNA content of exosomes released by beta-cells in physiological and physiopathological conditions was analyzed and the biological impact of their transfer to recipient cells investigated. Results Exosomes were isolated from the culture media of MIN6B1 and INS-1 derived 832/13 beta-cell lines and from mice, rat or human islets. Global profiling revealed that the microRNAs released in MIN6B1 exosomes do not simply reflect the content of the cells of origin. Indeed, while a subset of microRNAs was preferentially released in exosomes others were selectively retained in the cells. Moreover, exposure of MIN6B1 cells to inflammatory cytokines changed the release of several microRNAs. The dynamics of microRNA secretion and their potential transfer to recipient cells were next investigated. As a proof-of-concept, we demonstrate that if cel-miR-238, a C. Elegans microRNA not present in mammalian cells, is expressed in MIN6B1 cells a fraction of it is released in exosomes and is transferred to recipient beta-cells. Furthermore, incubation of untreated MIN6B1 or mice islet cells in the presence of microRNA-containing exosomes isolated from the culture media of cytokine-treated MIN6B1 cells triggers apoptosis of recipient cells. In contrast, exosomes originating from cells not exposed to cytokines have no impact on cell survival. Apoptosis induced by exosomes produced by cytokine-treated cells was prevented by down-regulation of the microRNA-mediating silencing protein Ago2 in recipient cells, suggesting that the effect is mediated by the non-coding RNAs. Conclusions Taken together, our results suggest that beta-cells secrete microRNAs that can be transferred to neighboring beta-cells. Exposure of donor cells to pathophysiological conditions commonly associated with diabetes modifies the release of microRNAs and affects survival of recipient beta-cells. Our results support the concept that exosomal microRNAs transfer constitutes a novel cell-to-cell communication mechanism regulating the activity of pancreatic beta-cells. Electronic supplementary material The online version of this article (doi:10.1186/s12964-015-0097-7) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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