4.7 Article

Tight junction disruption through activation of the PI3K/AKT pathways in the skin contributes to blister fluid formation after severe tibial plateau fracture

Journal

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fbioe.2022.946261

Keywords

tibial plateau fracture; fracture blisters; tight junctions; acute compartment syndrome; paracellular pathway

Funding

  1. Science and Technology Project of the Hebei Education Department [SLRC2019046]
  2. Government-funded Clinical Medicine Outstanding Talent Training Project
  3. National Natural Science Foundation of China [82072523, 82002281]
  4. Natural Science Foundation of Hebei [H2020206193, H2021206054]
  5. Main Medical Scientific Research of Hebei [20210543]
  6. China Postdoctoral Fund [2021 M701785]
  7. 14th Five-Year Clinical Medicine Innovation Research Team

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Acute compartment syndrome is an orthopedic emergency that often occurs after severe tibial plateau fracture. In this study, changes in tight junction expression in the skin after blister formation were observed. It was found that blistered skin is thinner and has significantly decreased levels of tight junction expression. This study suggests that changes in tight junction expression may contribute to blister fluid formation and the decrease in compartment pressure.
Background: Acute compartment syndrome (ACS) is an orthopedic emergency that commonly occurs after severe tibial plateau fracture. Fracture blisters form on the skin, and it was found in our previous study that when blisters form, the compartment pressure significantly decreases. However, the potential mechanism underlying this pressure decrease has not yet been elucidated. Methods: To obtain a comprehensive understanding of the changes that occur after blister formation on the skin, the changes in tight junction expression in the skin after tibial plateau fracture were observed. Blister samples and normal skin were collected from patients with bicondylar tibial plateau fractures with or without blisters. The epidermis thickness was measured, and the difference in the levels of K1, K5, K10, and skin barrier proteins such as claudin 1, claudin 2, and occludin between the two groups was evaluated by immunochemistry analysis, immunofluorescence, Western blotting, and qPCR. Results: The skin was thinner and the levels of K1, K5, and K10 were significantly decreased in blistered skin. Furthermore, the PI3K/AKT pathway was found to be activated, and the tight junction expression was significantly decreased in blistered skin. This indicates that the paracellular pathway, which is essential for accelerating fluid accumulation in blisters and indirectly decreases compartment pressure, was activated. Conclusion: Changes in the tight junction expression after blister formation may underlie blister fluid formation and indirectly explain the decrease in compartment pressure under blistered skin after severe tibial plateau fracture.

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