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Injured pancreatic ? cells enhance the release of miR-375-3p into the extracellular space.

ABSTRACT: miR-375-3p is a highly expressed microRNA in pancreatic ? cells. We have previously reported that when mice were exposed to 7 Gy X-ray irradiation, miR-375-3p was increased in the serum and there was cytotoxicity in pancreatic ? cells. However, it was unknown whether miR-375-3p is then released from injured pancreatic ? cells to the extracellular space. The present study investigated the effect of ionizing radiation and streptozotocin (STZ) treatment on the expression of extracellular miR-375-3p into culture supernatants using the rat pancreatic ? cell line RIN-5F. Cell growth was reduced, and cell death was increased at 24 h following exposure to 7 Gy irradiation as well as 24 h following treatment with 30 mM STZ compared with the control. Expression levels of miR-375-3p were significantly increased 24 h after 30 mM STZ treatment, yet this was only observed at 48 h following exposure to 7 Gy compared with the control. This suggests that the mechanism of cell death in RIN-5F is different between 7 Gy irradiation and 30 mM STZ treatment. The results of the present study suggest that injured pancreatic ? cells enhance the release of miR-375-3p from cells into extracellular space.

SUBMITTER: Chiba M

PROVIDER: S-EPMC6425272 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Injured pancreatic β cells enhance the release of miR-375-3p into the extracellular space.

Chiba Mitsuru M Niiyama Ikumi I Uehara Haruka H Kuwata Haruka H

Experimental and therapeutic medicine 20190213 4

miR-375-3p is a highly expressed microRNA in pancreatic β cells. We have previously reported that when mice were exposed to 7 Gy X-ray irradiation, miR-375-3p was increased in the serum and there was cytotoxicity in pancreatic β cells. However, it was unknown whether miR-375-3p is then released from injured pancreatic β cells to the extracellular space. The present study investigated the effect of ionizing radiation and streptozotocin (STZ) treatment on the expression of extracellular miR-375-3p ...[more]

PMID: 30930975

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Project description:IntroductionAnaphylaxis is among the most severe manifestations of allergic disorders, but its molecular basis remains largely unknown and reliable diagnostic markers are not currently available. MicroRNAs (miRNAs) regulate several pathophysiological processes and have been proposed as non-invasive biomarkers. Therefore, this study aims to evaluate their involvement in anaphylactic reaction and their value as biomarkers.MethodsAcute (anaphylaxis) and baseline (control) serum samples from 67 patients with anaphylaxis were studied. Among them, 35 were adults with drug-induced anaphylaxis, 13 adults with food-induced anaphylaxis and 19 children with food-induced anaphylaxis. The circulating serum miRNAs profile was characterized by next-generation sequencing (NGS). For this purpose, acute and baseline samples from 5 adults with drug-induced anaphylaxis were used. RNA was extracted, retrotranscribed, sequenced and the readings obtained were mapped to the human database miRBase_20. In addition, a system biology analysis (SBA) was performed with its target genes and revealed pathways related to anaphylactic mediators signaling. Moreover, functional and molecular endothelial permeability assays were conducted with miR-375-3p-transfected cells in response to cAMP.ResultsA total of 334 miRNAs were identified, of which 21 were significant differentially expressed between both phases. Extracellular vesicles (EVs) were characterized by Western blot, electron microscopy and NanoSight. A decrease of miR-375-3p levels was determined by qPCR in both serum and EVs of patients with anaphylaxis (****p<.0001). Precisely, the decrease of miR-375-3p correlated with the increase of two inflammatory cytokines: monocyte chemoattractant protein-1 (MCP-1) and granulocyte macrophage colony-stimulating factor (GM-CSF). On the other hand, functional and molecular data obtained showed that miR-375-3p partially blocked the endothelial barrier maintenance and stabilization by disassembly of cell-cell junctions exhibiting low Rac1-Cdc42 levels.DiscussionThese findings demonstrate a differential serum profile of circulating miRNAs in patients with anaphylaxis and exhibit the miR-375-3p modulation in serum and EVs during drug- and food-mediated anaphylactic reactions. Furthermore, the in silico and in vitro studies show a negative role for miR-375-3p/Rac1-Cdc42 in the endothelial barrier stability.

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Injured pancreatic ? cells enhance the release of miR-375-3p into the extracellular space.

Publications

Injured pancreatic β cells enhance the release of miR-375-3p into the extracellular space.

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