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Musculin Deficiency Aggravates Colonic Injury and Inflammation in Mice with Inflammatory Bowel Disease

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Abstract

Intestinal inflammatory reactions and resulting tissue injuries are two major aspects of inflammatory bowel disease (IBD). The regulatory factors involved in the pathogenesis of IBD remain unclear. Recent studies showed that musculin (MSC) as a transcription suppressor participates in the regulation of certain immune functions. The purpose of this study was to determine the impact of MSC deficiency on colonic injury and inflammatory reaction under IBD, where wild-type (WT, +/+) and MSC-knockout (MSCKO, MSC−/−) mice were induced for disease by dextran sulfate sodium (DSS) in drinking water. Immunohistochemistry hematoxylin-eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), and quantitative real-time polymerase chain reaction (qRT-PCR) were used to analyze the matching samples from groups of different genotypes. The colonic epithelial injury in the MSC−/− IBD group was much severer than that in the +/+ IBD group, concurrent with higher IL-22 levels from the supernatant of ex vivo cultured colon tissues in the MSC−/− IBD group than those in the +/+ IBD group. The mRNA levels of IL-22 in mesenteric lymph nodes (MLN) also manifested similar tendency. MSC deficiency may enhance the inflammatory reactions in the gut via excessive secretion of IL-22, leading to aggravated colonic epithelial injury under IBD.

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Acknowledgments

The authors would like to thank X Yan for editing the manuscript in English grammar and spelling. In addition, we also do appreciate Y S, W M, and X C for their kind statistical assistance and technological support.

Funding

This study was supported by the General Program of National Natural Science Foundation of China (81471863) (J Yan), the Special Project of Basic Science and Frontier Technology Research of Chongqing (cstc2016jcyjA0048) (J Yu), Natural Science Foundation of Chongqing (cstc 2018jcyjAX0258) (J Yan), and the Project for Enhancing Scientific and Technological Innovation Capabilities of Army Military Medical University (2019XYY22) (J Yan).

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Author notes

  1. Jing Yu and Yijia Liu contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical University (Third Military Medical University), No.10, Changjiang Branch Road, Yuzhong District, Chongqing, 400042, China

    Jing Yu, Yijia Liu, Xue Yang, Wanqi Tang, Huaping Liang & Jun Yan

  2. School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, Sichuan, China

    Yijia Liu & Suiyan Li

  3. Hainan Medical University, Haikou, 570100, Hainan, China

    Wei Zhang

  4. Antagen Institute for Biomedical Research, Boston, MA, 02118, USA

    Wenda Gao

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  1. Jing Yu
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Contributions

J Yan designed the study, performed data management, and drafted the paper. J Yu and YJ L participated in the study design and performed the experiments and data analysis. W Z, X Y, and WQ T performed the experiments. HP L and SY L participated in the study. W G designed the MSC−/− mouse, provided several important suggestions, and improved English writing of the paper. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jun Yan.

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The authors declare that they have no conflict of interest.

Ethics Approval

All animal procedures were conducted according to the guidelines and with the approval of the Army Medical University (Third Military Medical University) Laboratory Animal Management Committee and approved by the Ethics Committee.

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This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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Yu, J., Liu, Y., Zhang, W. et al. Musculin Deficiency Aggravates Colonic Injury and Inflammation in Mice with Inflammatory Bowel Disease. Inflammation 43, 1455–1463 (2020). https://doi.org/10.1007/s10753-020-01223-y

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  • DOI: https://doi.org/10.1007/s10753-020-01223-y

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