The Accumulation of Exosome-associated MicroRNA-1246 and MicroRNA-150-3p in Human Red Blood Cell Suspensions

Overview

Journal J Transl Med

Publisher Biomed Central

Specialties Biomedical Engineering
General Medicine

Date 2021 May 28

PMID 34044888

Citations 8

Authors

Yujie Kong

Xue Tian

Rui He

Chenyue Li

Haixia Xu

Li Tian

Zhong Liu

Affiliations

Soon will be listed here.

Abstract

Background: Transfusion-related immunomodulation (TRIM) can be caused by exosomes, in which case, microRNAs (miRNAs) are one critical factor impacting exosome behavior. This study aims to investigate and analyze the expression profiles of exosomal miRNA in red blood cell (RBC) suspensions during storage and to identify potential TRIM-related miRNAs as well as their potential functions.

Methods: A total of 25 packs of RBC suspensions were randomly collected. Exosome were extracted by ultracentrifugation and then identified and characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and western blot (WB). Exosomal miRNA profiles were acquired using gene chips in five packs on week 1 and week 5. The expression data were compared from the two time points identifying accumulated miRNAs with statistical significance and their predicted targeting genes were analyzed. Based on the gene chip results, quantitative reverse transcription-polymerase chain reactions (qRT-PCR) were performed to verify miRNA accumulation in the rest 20 packs sampling on week 1, 3 and 5.

Results: Gene chip analysis revealed that most exosomal miRNAs were enriched as the storage period progressed. Compared to samples from week 1, week 5 samples exhibited a total of 539 differential miRNA expressions, among which, 159 were statistically significant (P < 0.05) and 148 (93.08%) were accumulated. In the bioinformatics functional analysis, significant immunoregulatory annotations related to the thyroid hormone, mitogen-activated protein kinase (MAPK), focal adhesion and RAS signaling pathways were identified. The top 17 differential expression miRNAs were validated by qRT-PCR. The results confirmed that all the 17 miRNAs were accumulated with increasing storage time. In particular, miRNA-1246 and miRNA-150-3p were the most enriched strands by more than 150-folds in the 5-week storage period.

Conclusions: As storage progressed, numerous exosomal miRNAs accumulated in the RBC suspensions, which are informatically connected to multiple immuno-signaling pathways. MiRNA-1246 and miRNA-150-3p may be essential mediators impacting the immunoregulation functions of exosomes in RBC suspensions, considering their significant accumulating scales. Further research should therefore focus on the relationship between these miRNAs and TRIM.

Citing Articles

Measurement of α-synuclein as protein cargo in plasma extracellular vesicles.

Gilboa T, Ter-Ovanesyan D, Wang S, Whiteman S, Kannarkat G, Church G Proc Natl Acad Sci U S A. 2024; 121(45):e2408949121.

PMID: 39475636 PMC: 11551346. DOI: 10.1073/pnas.2408949121.

Human erythrocytes' perplexing behaviour: erythrocytic microRNAs.

Joshi U, Jani D, George L, Highland H Mol Cell Biochem. 2024; 480(2):923-935.

PMID: 39037663 DOI: 10.1007/s11010-024-05075-0.

MiR-33a-5p in stored red blood cells regulates genes of innate immune response and promotes inflammation.

Zhang J, Zhang D, Zhao J, Zheng W Aging (Albany NY). 2024; 16(12):10239-10251.

PMID: 38942609 PMC: 11236310. DOI: 10.18632/aging.205925.

Whispers in the Blood: Leveraging MicroRNAs for Unveiling Autologous Blood Doping in Athletes.

Hassanpour M, Salybekov A Int J Mol Sci. 2024; 25(1).

PMID: 38203416 PMC: 10779309. DOI: 10.3390/ijms25010249.

Apoptotic vesicles derived from human red blood cells promote bone regeneration via carbonic anhydrase 1.

Shao Y, Jiang Y, Yang K, Zhu Y, Liu Y, Zhang P Cell Prolif. 2023; 57(2):e13547.

PMID: 37697490 PMC: 10849785. DOI: 10.1111/cpr.13547.

References

Yoshida T, Prudent M, DAlessandro A . Red blood cell storage lesion: causes and potential clinical consequences. Blood Transfus. 2019; 17(1):27-52. PMC: 6343598. DOI: 10.2450/2019.0217-18. View

Almizraq R, Seghatchian J, Acker J . Extracellular vesicles in transfusion-related immunomodulation and the role of blood component manufacturing. Transfus Apher Sci. 2016; 55(3):281-291. DOI: 10.1016/j.transci.2016.10.018. View

Spinella P, Carroll C, Staff I, Gross R, Mc Quay J, Keibel L . Duration of red blood cell storage is associated with increased incidence of deep vein thrombosis and in hospital mortality in patients with traumatic injuries. Crit Care. 2009; 13(5):R151. PMC: 2784373. DOI: 10.1186/cc8050. View

Abdel-Latif G, Elwahab A, Hasan R, Elmongy N, Ramzy M, L Louka M . A novel protective role of sacubitril/valsartan in cyclophosphamide induced lung injury in rats: impact of miRNA-150-3p on NF-κB/MAPK signaling trajectories. Sci Rep. 2020; 10(1):13045. PMC: 7400763. DOI: 10.1038/s41598-020-69810-5. View

Vamvakas E . Pneumonia as a complication of blood product transfusion in the critically ill: transfusion-related immunomodulation (TRIM). Crit Care Med. 2006; 34(5 Suppl):S151-9. DOI: 10.1097/01.CCM.0000214310.70642.8C. View

Belizaire R, Prakash P, Richter J, Robinson B, Edwards M, Caldwell C . Microparticles from stored red blood cells activate neutrophils and cause lung injury after hemorrhage and resuscitation. J Am Coll Surg. 2012; 214(4):648-55. PMC: 4034387. DOI: 10.1016/j.jamcollsurg.2011.12.032. View

Burnouf T, Chou M, Goubran H, Cognasse F, Garraud O, Seghatchian J . An overview of the role of microparticles/microvesicles in blood components: Are they clinically beneficial or harmful?. Transfus Apher Sci. 2015; 53(2):137-45. DOI: 10.1016/j.transci.2015.10.010. View

Hess J . An update on solutions for red cell storage. Vox Sang. 2006; 91(1):13-9. DOI: 10.1111/j.1423-0410.2006.00778.x. View

Jara E, Munoz-Durango N, Llanos C, Fardella C, Gonzalez P, Bueno S . Modulating the function of the immune system by thyroid hormones and thyrotropin. Immunol Lett. 2017; 184:76-83. DOI: 10.1016/j.imlet.2017.02.010. View

10.

Guo Y, Pan W, Liu S, Shen Z, Xu Y, Hu L . ERK/MAPK signalling pathway and tumorigenesis. Exp Ther Med. 2020; 19(3):1997-2007. PMC: 7027163. DOI: 10.3892/etm.2020.8454. View

11.

Garcia-Roa M, Vicente-Ayuso M, Bobes A, Pedraza A, Gonzalez-Fernandez A, Martin M . Red blood cell storage time and transfusion: current practice, concerns and future perspectives. Blood Transfus. 2017; 15(3):222-231. PMC: 5448828. DOI: 10.2450/2017.0345-16. View

12.

Juffermans N, Vlaar A, Prins D, Goslings J, Binnekade J . The age of red blood cells is associated with bacterial infections in critically ill trauma patients. Blood Transfus. 2012; 10(3):290-5. PMC: 3417727. DOI: 10.2450/2012.0068-11. View

13.

Xu D, Fang X, Li Y, Zhang Z, Li Q . Perioperative blood transfusion is one of the factors that affect the prognosis of gastric cancer. J BUON. 2018; 23(3):672-677. View

14.

Zimring J, Spitalnik S . Pathobiology of transfusion reactions. Annu Rev Pathol. 2015; 10:83-110. DOI: 10.1146/annurev-pathol-012414-040318. View

15.

Qian M, Wang S, Guo X, Wang J, Zhang Z, Qiu W . Hypoxic glioma-derived exosomes deliver microRNA-1246 to induce M2 macrophage polarization by targeting TERF2IP via the STAT3 and NF-κB pathways. Oncogene. 2019; 39(2):428-442. DOI: 10.1038/s41388-019-0996-y. View

16.

Yu X, Odenthal M, Fries J . Exosomes as miRNA Carriers: Formation-Function-Future. Int J Mol Sci. 2016; 17(12). PMC: 5187828. DOI: 10.3390/ijms17122028. View

17.

Huang H, Zhu J, Fan L, Lin Q, Fu D, Wei B . MicroRNA Profiling of Exosomes Derived from Red Blood Cell Units: Implications in Transfusion-Related Immunomodulation. Biomed Res Int. 2019; 2019:2045915. PMC: 6595350. DOI: 10.1155/2019/2045915. View

18.

Downward J . Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer. 2003; 3(1):11-22. DOI: 10.1038/nrc969. View

19.

Sexton R, Mpilla G, Kim S, Philip P, Azmi A . Ras and exosome signaling. Semin Cancer Biol. 2019; 54:131-137. PMC: 6857536. DOI: 10.1016/j.semcancer.2019.02.004. View

20.

Blajchman M . Transfusion immunomodulation or TRIM: what does it mean clinically?. Hematology. 2005; 10 Suppl 1:208-14. DOI: 10.1080/10245330512331390447. View