Abstract
Previous studies have demonstrated that extracorporeal shock wave therapy (ESWT) could accelerate diabetic wound healing and that the inhibition of glycogen synthase kinase-3β (GSK-3β) 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-3β-mediated Wnt/β-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-3β inhibitor, to trigger Wnt/β-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 β-catenin expression showed significantly increased expression in the ESWT group. The IHC staining showed that Wnt-3a and -5a and β-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-3β-mediated Wnt/β-catenin signaling pathway.
Highlights
The in vivo results revealed that the size of the wound margin was significantly decreased in the extracorporeal shock wave therapy (ESWT)- and bromoindirubin-3 oxime (BIO)-treated diabetic groups compared with the diabetic control group (Figure 1a)
The results indicated that both ESWT and BIO enhanced diabetic wound healing
Wnt10 had an increasing trend, but the differences were not significant. These results demonstrated that ESWT enhanced diabetic wound healing and that wound healing was associated with the Wnt/β-catenin signaling pathway
Summary
Appropriate wound treatments include aggressive debridement, infection control, pressure offloading, and modern wound dressing [2]. Numerous therapeutic approaches have been developed to improve wound healing, such as hyperbaric oxygen therapy and negative pressure wound therapy [3]. These therapeutic options are useful adjuncts to standard treatment, some treatment outcomes remain unclear [4,5,6]. Extracorporeal shockwave therapy (ESWT) acts as a physical stimulus that promotes biological healing processes through mechanotransduction.
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