The Acceleration of Diabetic Wound Healing by Low-Intensity Extracorporeal Shockwave Involves in the GSK-3ß Pathway.

ABSTRACT

Previous studies have demonstrated that extracorporeal shock wave therapy (ESWT) could accelerate diabetic wound healing and that the inhibition of glycogen synthase kinase-3ß (GSK-3ß) is involved in epithelial differentiation during wound healing. This study investigated whether the enhancement of diabetic wound healing by ESWT is associated with the GSK-3ß-mediated Wnt/ß-catenin signaling pathway. A dorsal skin wounding defect model using streptozotocin-induced diabetic rodents was established. Rats were divided into 4 groups group 1, normal controls without diabetes; group 2, diabetic controls without treatment; group 3, diabetic rats receiving ESWT; and group 4, rats receiving 6-bromoindirubin-3'oxime (BIO), a GSK-3ß inhibitor, to trigger Wnt/ß-catenin signaling. Tissue samples were collected and analyzed by immunohistochemical (IHC) staining and quantitative RT-PCR. The ESWT and BIO-treated groups both exhibited significant promotion of wound healing compared to the healing in controls without treatment. RT-PCR analysis of Wnt-1, -3a, -4, -5a, and -10 and ß-catenin expression showed significantly increased expression in the ESWT group. The IHC staining showed that Wnt-3a and -5a and ß-catenin levels were significantly increased in the ESWT and BIO treatment groups compared to the control groups. ESWT enhancement of diabetic wound healing is associated with modulation of the GSK-3ß-mediated Wnt/ß-catenin signaling pathway.