Proteomic Analysis of Peri-Wounding Tissue Expressions in Extracorporeal Shock Wave Enhanced Diabetic Wound Healing in a Streptozotocin-Induced Diabetes Model

• Published in: International journal of molecular sciences 2020-07, Vol.21 (15), p.5445
• Main Authors: Chen, Rong-Fu, Yang, Ming-Yu, Wang, Ching-Jen, Wang, Chun-Ting, Kuo, Yur-Ren
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Cell growth; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - pathology; diabetic wound healing; Epidermal growth factor receptors; Extracorporeal Shockwave Therapy; Gene expression; Gene Expression Regulation - radiation effects; Glycoproteins; Hemopexin; Humans; Male; MAP kinase; Mass spectrometry; Mass spectroscopy; Musculoskeletal system; Peptides; Polymerase chain reaction; Proteinase; Proteins; Proteomes; Proteomics; Rats; Real time; Receiving; Scientific imaging; Serine; Serine proteinase; Serine proteinase inhibitors; serpin; shock wave; Skin - metabolism; Skin - pathology; Skin - radiation effects; Streptozocin; Studies; Ulcers; Wound healing; Wound Healing - genetics; Wound Healing - radiation effects
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21155445

Our former studies have demonstrated that extracorporeal shock wave therapy (ESWT) could enhance diabetic wound healing but the bio-mechanisms remain elusive. This study investigated the changes of topical peri-wounding tissue expressions after ESWT in a rodent streptozotocin-induced diabetic wounding model by using the proteomic analysis and elucidated the molecular mechanism. Diabetic rats receiving ESWT, normal control, and diabetic rats receiving no therapy were analyzed. The spots of interest in proteome analysis were subjected to mass spectrometry to elucidate the peptide mass fingerprints. Protein expression was validated using immunohistochemical staining and related expression of genes were analyzed using real-time RT-PCR. The proteomic data showed a significantly higher abundance of hemopexin at day 3 of therapy but down-regulation at day 10 as compared to diabetic control. In contrast, the level of serine proteinase inhibitor (serpin) A3N expression was significantly decreased at day 3 therapy but expression was upregulated at day 10. Using real-time RT-PCR revealed that serpin-related EGFR-MAPK pathway was involved in ESWT enhanced diabetic wound healing. In summary, proteome analyses demonstrated the expression change of hemopexin and serpin with related MAPK signaling involved in ESWT-enhanced diabetic wound healing. Modulation of hemopexin and serpin related pathways are good strategies to promote wound healing.