Journal
MICROVASCULAR RESEARCH
Volume 132, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mvr.2020.104067
Keywords
Burn injury; Edema; Angiogenesis; Tight junction; Cingulin; Mouse model; Vascular barrier; Wound healing; Vessel dilation
Categories
Funding
- Vienna Science and Technology fund WWTF [LS18-080]
- Swiss National Foundation for Scientific Research [N. 31003A-103637, N. 31003A-116763, N. 31003A_133158]
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Edema formation due to the collapse of physiological barriers and the associated delayed healing process is still a central problem in the treatment of burn injuries. In healthy individuals, tight junctions form a barrier to fluid and small molecules. Cingulin is a cytoplasmic component of tight junctions and is involved in the regulation of the paracellular barrier. Endothelial specific cingulin knock-out mice provide new insight into the influence of tight junction proteins on edema formation and angiogenesis during wound healing. Knock-out mice lacking the head domain of cingulin in endothelial cells (Cgn(Delta EC)) were created by breeding Cgn(fl/fl) mice with Tie1-cre mice. Using a no-touch hot air jet a burn trauma was induced on the ear of the mouse. Over a period of 12 days microcirculatory parameters such as edema formation, angiogenesis and leukocyte-endothelial interactions were visualized using intravital fluorescence microscopy. At baseline, Cgn(Delta EC) mice surprisingly showed significantly less tracer extravasation compared to Cgn(fl/fl) littermates, whereas, after burn injury, edema was consistently higher in Cgn(Delta EC) mice. Non-perfused area after wounding was increased, but there was no difference in vessel diameters, contraction or dilation of arteries in Cgn(Delta EC) mice. Moreover, cingulin knock-out did not cause a difference in leukocyte adhesion after burn injury. In summary, cingulin limits non-perfused area after burn injury and maintains the paracellular barrier of blood vessels. Since edema formation with serious systemic effects is a central problem of burn wounds, understanding the importance of tight junction proteins might help to find new treatment strategies for burn wounds.
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