The Acceleration of Diabetic Wound Healing by Low-Intensity Extracorporeal Shockwave Involves in the GSK-3β Pathway
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...
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MDPI AG
2020-12-01
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author | Rong-Fu Chen Yun-Nan Lin Keng-Fan Liu Chun-Ting Wang Savitha Ramachandran Ching-Jen Wang Yur-Ren Kuo |
author_facet | Rong-Fu Chen Yun-Nan Lin Keng-Fan Liu Chun-Ting Wang Savitha Ramachandran Ching-Jen Wang Yur-Ren Kuo |
author_sort | Rong-Fu Chen |
collection | DOAJ |
description | 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. |
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spelling | doaj.art-902445b741b04647b4343b7eee4ad4822023-11-21T03:02:43ZengMDPI AGBiomedicines2227-90592020-12-01912110.3390/biomedicines9010021The Acceleration of Diabetic Wound Healing by Low-Intensity Extracorporeal Shockwave Involves in the GSK-3β PathwayRong-Fu Chen0Yun-Nan Lin1Keng-Fan Liu2Chun-Ting Wang3Savitha Ramachandran4Ching-Jen Wang5Yur-Ren Kuo6Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanDivision of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanDivision of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanDivision of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanDepartment of Plastic and Reconstructive Surgery, KK Women’s and Children’s Hospital, Singapore 229899, SingaporeDepartment of Orthopaedics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanDivision of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanPrevious 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.https://www.mdpi.com/2227-9059/9/1/21diabetic wound healingGSK-3ββ-cateninBIOWntextracorporeal shockwave therapy |
spellingShingle | Rong-Fu Chen Yun-Nan Lin Keng-Fan Liu Chun-Ting Wang Savitha Ramachandran Ching-Jen Wang Yur-Ren Kuo The Acceleration of Diabetic Wound Healing by Low-Intensity Extracorporeal Shockwave Involves in the GSK-3β Pathway Biomedicines diabetic wound healing GSK-3β β-catenin BIO Wnt extracorporeal shockwave therapy |
title | The Acceleration of Diabetic Wound Healing by Low-Intensity Extracorporeal Shockwave Involves in the GSK-3β Pathway |
title_full | The Acceleration of Diabetic Wound Healing by Low-Intensity Extracorporeal Shockwave Involves in the GSK-3β Pathway |
title_fullStr | The Acceleration of Diabetic Wound Healing by Low-Intensity Extracorporeal Shockwave Involves in the GSK-3β Pathway |
title_full_unstemmed | The Acceleration of Diabetic Wound Healing by Low-Intensity Extracorporeal Shockwave Involves in the GSK-3β Pathway |
title_short | The Acceleration of Diabetic Wound Healing by Low-Intensity Extracorporeal Shockwave Involves in the GSK-3β Pathway |
title_sort | acceleration of diabetic wound healing by low intensity extracorporeal shockwave involves in the gsk 3β pathway |
topic | diabetic wound healing GSK-3β β-catenin BIO Wnt extracorporeal shockwave therapy |
url | https://www.mdpi.com/2227-9059/9/1/21 |
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