Annexin A1(2-26) Treatment Improves Skin Heterologous Transplantation by Modulating Inflammation and Angiogenesis Processes

Author(s)

Lacerda, Jessica Zani ^[1] ; Drewes, Carine Cristiane ^[2] ; Oliveira Mimura, Kallyne Kioko ^[3] ; Zanon, Caroline de Freitas ^[1] ; Ansari, Tahera ^[4] ; Gil, Cristiane Damas ^[3] ; Greco, Karin Vicente ^[4] ; Poliselli Farsky, Sandra Helena ^[2] ; Oliani, Sonia Maria ^{[1, 3]}

Affiliation

^[1] Sao Paulo State Univ, UNESP, Inst Biosci Humanities & Exact Sci IBILCE, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Struct & Funct Biol, Sao Paulo - Brazil

^[4] UCL, Northwick Pk Inst Med Res, Dept Surg Res, London - England

• Document type: Journal article
• Source: FRONTIERS IN PHARMACOLOGY; v. 9, SEP 10 2018.
• Web of Science Citations: 1

Abstract

Skin graft successful depends on reduction of local inflammation evoked by the surgical lesion and efficient neovascularization to nutrition the graft. It has been shown that N-terminal portion of the Annexin A1 protein (AnxA1) with its anti-inflammatory properties induces epithelial mucosa repair and presents potential therapeutic approaches. The role of AnxA1 on wound healing has not been explored and we investigated in this study the effect of the peptide Ac2-26 (N-terminal AnxA1 peptide Ac2-26; AnxA1(2-26)) on heterologous skin scaffolds transplantation in BALB/c mice, focusing on inflammation and angiogenesis. Treatment with AnxA1(2-26), once a day, from day 3-60 after scaffold implantation improved the take of the implant, induced vessels formation, enhanced gene and protein levels of the vascular growth factor-A (VEGF-A) and fibroblast influx into allograft tissue. It also decreased pro-while increasing anti-inflammatory cytokines. The pro-angiogenic activity of AnxA1(2-26) was corroborated by topical application of AnxA1(2-26) on the subcutaneous tissue of mice. Moreover, treatment of human umbilical endothelial cells (HUVECs) with AnxA1(2-26) improved proliferation, shortened cycle, increased migration and actin polymerization similarly to those evoked by VEGF-A. The peptide treatment instead only potentiated the tube formation induced by VEGF-A. Collectively, our data showed that AnxA1(2-26) treatment favors the tissue regeneration after skin grafting by avoiding exacerbated inflammation and improving the angiogenesis process. (AU)

• FAPESP's process: 13/07487-2 - Investigation of the action of annexin a1 protein on the angiogenesis process induced by vascular endothelial growth factor: experimental models in vivo and in vitro
• Grantee: Jéssica Zani Lacerda
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 12/13041-4 - Evaluation of skin heterologous graft using acellular matrices obtained from porcine skin and annexin A1 action as anti-inflammatory / immunosuppressive agent.
• Grantee: Kallyne Kioko Oliveira Mimura
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/21603-2 - Tissue bioengineering: evaluate skin xenograft using porcine acellular matrices and effect of annexin A1 protein as a therapeutic approach in the regenerative and wound healing processes
• Grantee: Sonia Maria Oliani
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/02012-4 - Evaluation of the immunomodulatory activity of annexin A1 protein in the regulation of inflammatory disorders of the gastrointestinal system: studies in vivo and in vitro experimental models
• Grantee: Sonia Maria Oliani
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/19802-1 - Effects of lipid-core nanocapsules with acetyleugenol in melanomas: in vivo and in vitro studies
• Grantee: Carine Cristiane Drewes
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/07328-4 - Identification of endogenous pathways for the control of inflammation
• Grantee: Sandra Helena Poliselli Farsky
• Support Opportunities: Research Projects - Thematic Grants