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MiR155 Disrupts the Intestinal Barrier by Inducing Intestinal Inflammation and Altering the Intestinal Microecology in Severe Acute Pancreatitis

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Abstract

Background

Intestinal dysfunction is a common complication of acute pancreatitis. MiR155 may be involved in the occurrence and development of intestinal dysfunction mediated by acute pancreatitis, but the specific mechanism is not clear.

Aims

To investigate the effect of miR155 on severe acute pancreatitis (SAP)-associated intestinal dysfunction and its possible mechanism in a mice model.

Methods

In this study, SAP mice model was induced by intraperitoneal injection of caerulein and LPS in combination. Adeno-associated virus (AAV) was given by tail vein injection before the SAP model. The pancreatic and intestinal histopathology changes were analyzed. Cecal tissue was collected for 16S rRNA Gene Sequencing. Intestinal barrier proteins ZO-1 and E-cad were measured by Immunohistochemistry Staining and Western Blot, respectively. Intestinal tissue miR155 and inflammatory factors TNF-α, IL-1β, and IL-6 were detected by Q-PCR. The expression levels of protein associated with TNF-α and TLR4/MYD88 pathway in the intestinal were detected.

Results

In miR155 overexpression SAP group, the levels of tissue inflammatory factor were significantly increased, intestinal barrier proteins were significantly decreased, and the injury of intestinal was aggravated. Bacterial 16S rRNA sequencing was performed, showing miR155 promotes gut microbiota dysbiosis. The levels of TNF-α, TLR4, and MYD88 in the intestinal were detected, suggesting that miR155 may regulate gut microbiota and activate the TLR4/MYD88 pathway, thereby affecting the release of inflammatory mediators and regulating SAP-related intestinal injury. After application of miR155-sponge, imbalance of intestinal flora and destruction of intestinal barrier-related proteins have been alleviated. The release of inflammatory mediators decreased, and the histopathology injury of intestinal was improved obviously.

Conclusion

MiR155 may play an important role in SAP-associated intestinal dysfunction. MiR155 can significantly alter the intestinal microecology, aggravated intestinal inflammation through TLR4/MYD88 pathway, and disrupts the intestinal barrier in SAP mice.

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Abbreviations

SAP:

Severe acute pancreatitis

TLR:

Toll-like receptors

IP:

Intraperitoneal

MYD88:

Myeloid differentiation factor 88

AAV:

Adeno-associated virus

CON:

Control group

CAE-LPS:

Caerulein + LPS treatment

CAE-LPS-miR155-O/E or CAE-LPS-miR155:

Caerulein + LPS + miR155 overexpression treatment

CAE-LPS-miR155-sponge:

Caerulein + LPS + miR155 sponge treatment

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Acknowledgments

The National Natural Science Foundation of China (Nos: 81460130 and 81760121), Funding scheme for outstanding young talents in Jiangxi province (20192BCB23021), and the Graduate Innovation Fund of Nanchang University (No. CX2018231) supported this study together.

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Author notes

  1. Xiaoyu Yang and Jianhua Wan have equally contributed to this work.

Authors and Affiliations

  1. Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, People’s Republic of China

    Xiaoyu Yang, Jianhua Wan, Nianshuang Li, Cong He, Yue Zhang, Xueyang Li, Yin Zhu & Liang Xia

  2. Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, USA

    Jianhua Wan

  3. Department of Rheumatology, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China

    Yuping Ren

  4. Department of Intensive Care Unit, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China

    Fen Liu

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  1. Xiaoyu Yang
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Contributions

JW, XY, and LX contributed to conception and design of the study; XY and JW performed experiment; NSL, CH, YZ, YR, XL, and YZ performed the data analysis; XY and JW drafted the manuscript; NHL and LX performed critical revision of the manuscript; JW, FL, and NHL contributed to reagents/materials/analysis tools; and all authors contributed to manuscript revision and read and approved the submitted version.

Corresponding author

Correspondence to Liang Xia.

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10620_2021_7022_MOESM1_ESM.pdf

Intestinal barrier destruction and elevated miR155 in mice with SAP (n = 8 for each group). (A) Pancreatic and intestine histology in BALB/c mice. (B) pathology score of intestine. (C) The expression of miR155 and (D) inflammatory index in intestine was shown. Control (CON): saline treatment. CAE+LPS: caerulein +LPS treatment. Data shown are means ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 (PDF 585 kb)

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Yang, X., Wan, J., Li, N. et al. MiR155 Disrupts the Intestinal Barrier by Inducing Intestinal Inflammation and Altering the Intestinal Microecology in Severe Acute Pancreatitis. Dig Dis Sci 67, 2209–2219 (2022). https://doi.org/10.1007/s10620-021-07022-1

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