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Burn-Induced Impairment of Ileal Muscle Contractility Is Associated with Increased Extracellular Matrix Components

  • 2019 SSAT Plenary Presentation
  • Published:
Journal of Gastrointestinal Surgery

Abstract

Introduction

Severe burns lead to marked impairment of gastrointestinal motility, such as delayed gastric emptying and small and large intestinal ileus. However, the cellular mechanism of these pathologic changes remains largely unknown.

Methods

Male Sprague Dawley rats approximately 3 months old and weighing 300–350 g were randomized to either a 60% total body surface area full-thickness scald burn or sham procedure and were sacrificed 24 h after the procedure. Gastric emptying, gastric antrum contractility ileal smooth muscle contractility, and colonic contractility were measured. Muscularis externa was isolated from the ileal segment to prepare smooth muscle protein extracts for Western blot analysis.

Results

Compared with sham controls, the baseline rhythmic contractile activities of the antral, ileal, and colonic smooth muscle strips were impaired in the burned rats. Simultaneously, our data showed that ileal muscularis ECM proteins fibronectin and laminin were significantly up-regulated in burned rats compared with sham rats. TGF-β signaling is an important stimulating factor for ECM protein expression. Our results revealed that TGF-β signaling was activated in the ileal muscle of burned rats evidenced by the activation of Smad2/3 expression and phosphorylation. In addition, the total and phosphorylated AKT, which is an important downstream factor of ECM signaling in smooth muscle cells, was also up-regulated in burned rats’ ileal muscle. Notably, these changes were not seen in the colonic or gastric tissues.

Conclusion

Deposition of fibrosis-related proteins after severe burn is contributors to decreased small intestinal motility.

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Authors and Affiliations

  1. Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA

    Claire B. Cummins, Xiaofu Wang & Ravi S. Radhakrishnan

  2. Department of Neuroscience, University of Texas Medical Branch, Galveston, TX, USA

    Yanping Gu

  3. Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA

    You-Min Lin & Xuan-Zheng Shi

  4. Departments of Pediatrics and Surgery, 301 University Blvd., Galveston, TX, 77555-0353, USA

    Ravi S. Radhakrishnan

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  1. Claire B. Cummins
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  2. Yanping Gu
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  3. Xiaofu Wang
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  4. You-Min Lin
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  5. Xuan-Zheng Shi
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  6. Ravi S. Radhakrishnan
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Contributions

CBC, YG, XW, YL, XS, and RSR conceived of and designed this work. CBC, XW, YL, and XS conducted the experiments. CBC drafted the manuscript. CBC, YG, XW, YL, XS, and RSR critically reviewed the manuscript, provided approval of the final version, and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Ravi S. Radhakrishnan.

Ethics declarations

All animal research procedures adhered to the National Institutes of Health guidelines for experimental animal use and were approved by the Institutional Animal Care and Use Committee at the University of Texas Medical Branch at Galveston, TX (Protocol # 1509059).

Conflict of Interest

The authors declare that they have no conflicts of interest.

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This paper was presented as a plenary presentation through the Surgical Society for the Alimentary Tract at Digestive Disease Week on May 21, 2019.

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Cummins, C.B., Gu, Y., Wang, X. et al. Burn-Induced Impairment of Ileal Muscle Contractility Is Associated with Increased Extracellular Matrix Components. J Gastrointest Surg 24, 188–197 (2020). https://doi.org/10.1007/s11605-019-04400-z

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