Modulation of vascular endothelial growth factor and mitogen‐activated protein kinase‐related pathway involved in extracorporeal shockwave therapy accelerate diabetic wound healing

Abstract

Extracorporeal shockwave therapy (ESWT) has a significant positive effect to accelerate chronic wound healing. This study investigated whether the vascular endothelial growth factor (VEGF)–related pathway has involved in ESWT enhancement of diabetic wound healing. A dorsal skin defect (area, 6 × 5 cm) in a streptozotocin‐induced diabetes rodent model was used. Thirty‐two male Wistar rats were divided into four groups. Group I consisted of nondiabetic control; group II, diabetic control without treatment; group III, diabetic rats received ESWT; and group IV, rats received Avastin (a VEGF monoclonal antibody) on day 0 (post‐wounding immediately) to day 7 and ESWT on day 3 and day 7. The wound healing was assessed clinically. The VEGF, endothelial nitric oxide synthase (eNOS), and Ki‐67 were analyzed with immunohistochemical staining. The mRNA expression of mitogen‐activated protein kinase–related genes was measured by real‐time quantitative real‐time polymerase chain reaction. The results revealed wound size was significantly reduced in the ESWT‐treated rats as compared to the diabetic control (p < 0.01). The positive effect of ESWT‐increasing wound healing was significantly suppressed in pretreatment of the Avastin group. Histological findings revealed significant increase in neo‐vessels in the ESWT group as compared to the control. In immunohistochemical stain, significant increases in VEGF, eNOS, and Ki‐67 expressions were noted in the ESWT group as compared to that in controls. However, Avastin suppressed the shockwave effect and down‐regulation of VEGF, eNOS, and Ki‐67 expressions in the Avastin‐ESWT group as compared to that in the ESWT alone group. We found that highly mRNA expression of Kras, Raf1, Mek1, Jnkk, Jnk, and Jun at early stage in the ESWT group, as compared to the diabetic control. These evidences indicated treatment with multiple sessions of ESWT significantly enhanced diabetic wound healing associated with increased neovascularization and tissue regeneration. The bio‐mechanism of ESWT‐enhanced wound healing is correlated with VEGF and mitogen‐activated protein kinase–mediated pathway.

Identification of Hub Genes and Key Pathways Associated with Atopic Dermatitis via Integrated Bioinformatics

“…The mRNA expression of KRAS was observed in diabetic wound healing model with extracorporeal shockwave therapy in comparison with diabetic control. The result also confirmed the correlation with vascular endothelial growth factor (VEGF) which could be regarded as a potentially important mediator in the pathogenesis of AD [22,23]. Since the similarity of the healing process of skin lesion between diabetes and AD, KRAS could be used as a target for skin lesion healing in AD.…”

“…The top 50 target proteins in each mentioned algorism had been integrated for key hub genes. The 23 VDR (degree value: 19), KIT (24), BCL2L11 (16), NFKBIA (22), KRAS (30), IL13 (37), JAK2 (35), STAT3…”

Supercritical Carbon Dioxide-decellularized Porcine Acellular Dermal Matrix combined with Autologous Adipose-derived Stem Cells: Its Role in Accelerated Diabetic Wound Healing

“…In the present investigation, EGF expression was elevated in the group with the DM wound treated with ADM-ASCs (DM + A/A), indicating epidermal regeneration and anti-inflammation in diabetic wound healing. VEGF is an important regulator of pathophysiological angiogenesis and vascular development in wound healing [57]. VEGF expression was found elevated in the early phase of wound healing then followed with a decrease in the late phase [58][59][60].…”

Improved Healing of Diabetic Foot Ulcer upon Oxygenation Therapeutics through Oxygen-Loading Nanoperfluorocarbon Triggered by Radial Extracorporeal Shock Wave

“…The radial extracorporeal shock wave therapy (rESWT) has been widely applied in musculoskeletal disorders, myocardial infarction, wound healing, and erectile dysfunction due to the noninvasive mode of treatment, cost effectiveness, lower energy level, and negligible side effects [27][28][29]. More importantly, rESW is a type of pneumatically generated pressure wave [30,31] that can induce the cavitation effect, which refers to the rapid formation, expansion, and collapse of small vapor bubbles in liquids due to sharp pressure changes [32][33][34].…”