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

• Main Authors: Rong-Fu Chen, Yun-Nan Lin, Keng-Fan Liu, Chun-Ting Wang, Savitha Ramachandran, Ching-Jen Wang, Yur-Ren Kuo
• Format: Article
• Language: English
• Published: MDPI AG 2021-12-01
• Series: Biomedicines
• Subjects: diabetic wound healing; GSK-3β; β-catenin; BIO; Wnt; extracorporeal shockwave therapy
• Online Access: https://www.mdpi.com/2227-9059/9/1/21

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.