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Inhibition of miR-1298-5p attenuates sepsis lung injury by targeting SOCS6

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Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Sepsis is one of the leading causes of morbidity and mortality and a major cause of acute lung injury (ALI). carried by exosomes play a role in a variety of diseases. However,there are not many studies of exosomal miRNAs in sepsis and sepsis lung injury.miR-1298-5p and suppressor of cytokine signaling 6 (SOCS6) were silenced or overexpressed in human bronchial epithelial cells (BEAS-2B). PKH-67 Dye was used to trace exosome endocytosis. Cell permeability was evaluated by measuring trans-epithelial electrical resistance (TEER) and FITC dextran flux. ELISA kits were used for cytokine detection. Quantitative RT-PCR and western blots were used to evaluate gene expression. miR-1298-5p was elevated in exosomes from patients with sepsis lung injury (Sepsis_exo). Treatment of BEAS-2B cells using Sepsis_exo significantly inhibited cell proliferation, and induced cell permeability and inflammatory response. miR-1298-5p directly targeted SOCS6. Overexpressing SOCS6 reversed miR-1298-5p-induced cell permeability and inflammatory response. Inhibition of STAT3 blocked SOCS6-silencing caused significant increase of cell permeability and inflammation. Exosomes isolated from patients of sepsis lung injury increased cell permeability and inflammatory response in BEAS-2B cells through exosomal miR-1298-5p which targeted SOCS6 via STAT3 pathway. The findings highlight the importance of miR-1298-5p/SOCS6/STAT3 axis in sepsis lung injury and provide new insights into therapeutic strategies for sepsis lung injury.

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All data generated or analyzed during this study are included in this published article.

Abbreviations

ALI:

Acute lung injury

miRNAs:

MicroRNAs

SOCS6:

Suppressor of cytokine signaling 6

TEER:

Trans-epithelial electrical resistance

Sepsis_exo:

Exosomes from patients with sepsis lung injury

CIS:

Cytokine-inducible SH2-containing protein

STAT3:

Signal transducer and activator of transcription 3

EVs:

Extracellular vesicles

GC:

Gastric cancer

IBD:

Inflammatory bowel disease

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Acknowledgement

We would like to thank TopEdit (www.topeditsci.com) for English language editing of this manuscript.

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Authors and Affiliations

  1. Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Doctor’s Office, 10th floor, building 2, NO.507 Zhengmin Road, Yangpu District, Shanghai, 200433, P.R. China

    Jian Ma, Li-Yun Xu, Qiu-Hong Sun, Xiao-Yu Wan &  BingLi

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Contributions

J.M. designed this projected and wrote the manuscript; J.M., L.Y.X. performed the experiments; Q.H.S., X.Y.W., B.L. analyzed the data and edited diagrams. All authors have contributed to, read, and agreed upon the final contents of the manuscript for submission.

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Correspondence to Jian Ma.

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The protocol for the present study was approved by the Ethics Committee of Shanghai Pulmonary Hospital (Shanghai, China), and it conforms to the provisions of the Declaration of Helsinki in 1995. All participants have provided their written informed consent to participate in the study.

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Ma, J., Xu, LY., Sun, QH. et al. Inhibition of miR-1298-5p attenuates sepsis lung injury by targeting SOCS6. Mol Cell Biochem 476, 3745–3756 (2021). https://doi.org/10.1007/s11010-021-04170-w

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