System of plasminogen regulators in the skin of intact uPA gene-knockout C57BL/6-PlautmI.IBug-This Plau6FDhu/GFDhu mice and in a model of chronic neurogenic pain

Purpose of the study. Studying the components of the cascade of plasminogen (PG) regulator in the skin of intact uPA (urokinase plasminogen activator) gene-knockout mice and in a model of chronic neurogenic pain (CNP).

Materials and methods. The study included 76 mice divided in groups depending on the gender, presence or absence of uPA gene knockout and CNP. A CNP model was created by sciatic nerve ligation; levels and activity of components of PG activation cascade were studied by ELISA using standard test systems.

Results. Intact uPA-deficient C57BL/6-PlautmI.IBug-ThisPlau6FDhu/GFDhu mice differed from C57BL/6 mice by a decreased level of PG regulators, excluding plasmin in all mice, PG in males and urokinase receptor (uPAR). uPA-deficient mice with CNP showed continuing decrease in levels of plasminogen regulators, except for uPAR in all mice, PG in males and the activity of plasminogen activator inhibitor-1 (PAI-1-act) in females.

Conclusion. Almost the entire cascade of PG regulators was inhibited in intact uPA-deficient mice of both genders, compared to C57BL/6 animals, except for uPAR in females, PG in males and plasmin in all animals. In CNP, PG regulators in uPA-deficient mice were inhibited compared to the background, excluding uPAR in males and females. The comparison with C57BL/6 mice demonstrated that the CNP model resulted in the uPA system state very similar to that in intact uPA-deficient C57BL/6-PlautmI.IBug-ThisPlau6FDhu/GFDhu animals. In C57BL/6 mice with CNP, levels of uPA were reduced by 2 orders of magnitude, relative to the norm, with the almost complete depletion of uPA activity. uPA gene knockout results in a persistent suppression of the system of PG regulators which is practically not affected by CNP, except for the uPAR level, and causes changes similar to that in the CNP modeling in normal mice.

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