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MicroRNA-483-3p Inhibitor Ameliorates Sepsis-Induced Intestinal Injury by Attenuating Cell Apoptosis and Cytotoxicity Via Regulating HIPK2

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Abstract

Sepsis is a life-threatening syndrome that can result in multi-organ dysfunction. MicroRNA (miR)-483-3p was previously demonstrated to be upregulated in sepsis patients; however, its specific functions in sepsis-triggered intestinal injury remain unclarified. Human intestinal epithelial NCM460 cell line was stimulated with lipopolysaccharide (LPS) to mimic sepsis-induced intestinal injury in vitro. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining was utilized for examining cell apoptosis. Western blotting and real time quantitative polymerase chain reaction (RT-qPCR) were used for detecting molecular protein and RNA levels. LPS-induced cytotoxicity was determined by measuring concentrations of lactate dehydrogenase (LDH), diamine oxidase (DAO) and fatty acid binding protein 2 (FABP2). Luciferase reporter assay was utilized for verifying the interaction between miR-483-3p and homeodomain interacting protein kinase 2 (HIPK2). Inhibiting miR-483-3p alleviates LPS-triggered NCM460 cell apoptosis and cytotoxicity. miR-483-3p targeted HIPK2 in LPS-stimulated NCM460 cells. Knockdown of HIPK2 reversed the above effects mediated by miR-483-3p inhibitor. Inhibiting miR-483-3p ameliorates LPS-triggered apoptosis and cytotoxicity by targeting HIPK2.

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Data Availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

Not applicable.

Funding

This work was supported by Natural Science Research Project of Colleges and Universities in Anhui Province (Grant no. KJ2021ZD0099) and Horizontal Scientific Research Project of Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College (Grant no. 662202204007).

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  1. Zhen Wang and Xuemei Qin have contributed equally to this work.

Authors and Affiliations

  1. Department of General Practice, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China

    Zhen Wang

  2. Department of Critical Care Medicine, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China

    Xuemei Qin, Jin Yuan, Hongzhen Yin, Rui Qu & Changshun Zhong

  3. Department of Burn and Plastic Surgery, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, No 2, Zheshan West Rd, Wuhu, 241000, Anhui, China

    Wei Ding

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Contributions

ZW and XQ: conceived and designed the experiments. ZW, XQ, JY, HY, RQ, CZ and WD: carried out the experiments. ZW, XQ and WD: drafted the manuscript. All authors have read and approved the final manuscript.

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Correspondence to Wei Ding.

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Wang, Z., Qin, X., Yuan, J. et al. MicroRNA-483-3p Inhibitor Ameliorates Sepsis-Induced Intestinal Injury by Attenuating Cell Apoptosis and Cytotoxicity Via Regulating HIPK2. Mol Biotechnol 66, 233–240 (2024). https://doi.org/10.1007/s12033-023-00734-x

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