Recombinant Protein rP21 from Trypanosoma cruzi has Effect on Inflammation, Angiogenesis and Fibrogenesis in Skin Wound Model C57BL/6 Mouse
-
Jeranice Silva Barbosa
-
Francyelle Borges Rosa de Moura
-
Bruno Antonio Ferreira
-
Flávia Alves Martins
-
Elusca Helena Muniz
-
José Augusto Leoncio Gomide
-
Cláudio Vieira da Silva
-
Daniele Lisboa Ribeiro
-
Fernanda de Assis Araújo
-
Tatiana Carla Tomiosso
Advances in Research,
Page 28-37
DOI:
10.9734/air/2021/v22i130285
Abstract
Aims: Recombinant proteins rP2 has demonstrated biological activity in inflammation by acting on the recruitment of leukocytes and by inducing phagocytosis, also modulating the processes of angiogenesis and fibrogenesis in different experimental models. In this study we evaluated the effects of the recombinant protein rP21 from Trypanosama cruzi in cutaneous wounds.
Study Design: The wounds were induced on the back of mice and treated with rP21 at 1 µg/mL and 50 µg/mL concentration, for 3 and 7 days.
Study Location and Duration: Institute of Biomedical Sciences and Animal Breeding Network and Rodents of the Federal University of Uberlândia, between February 2015 and February 2016.
Methodology: The contraction time of wound, inflammatory cell activities (neutrophils and macrophages), angiogenesis and local collagen density were evaluated.
Sample: Wound induction was performed on 64 male BALB / c mice approximately 9 weeks old.
Results: Wounds treated with rP21 showed less closure time, in addition to exhibiting greater neutrophil activity in the initial phasis, which was reduced simultaneously with the increased macrophage activity. The rP21 also performed pro-angiogenic and pro-fibrogenic activity in this study model.
Conclusion: These results demonstrate for the first time the biological potential of rP21 in accelerating skin tissue repair.
Keywords:
- Angiogenesis
- healing
- inflammation
- recombinant protein
- skin.
How to Cite
Barbosa, J. S., Moura, F. B. R. de, Ferreira, B. A., Martins, F. A., Muniz, E. H., Gomide, J. A. L., Silva, C. V. da, Ribeiro, D. L., Araújo, F. de A., & Tomiosso, T. C. (2021). Recombinant Protein rP21 from Trypanosoma cruzi has Effect on Inflammation, Angiogenesis and Fibrogenesis in Skin Wound Model C57BL/6 Mouse. Advances in Research, 22(1), 28-37. https://doi.org/10.9734/air/2021/v22i130285
References
Cañedo-Dorantes L, Cañedo-Ayala M. Skin acute wound healing: A comprehensive review. Int J Inflam; 2019.
Yin H, Chen CY, Liu YW, et al. Synechococcus elongatus PCC7942 secretes extracellular vesicles to accelerate cutaneous wound healing by promoting angiogenesis. Theranostics 2019;9:2678–2693.
Barrientos S, Brem H, Stojadinovic O, et al. Clinical application of growth factors and cytokines in wound healing. Wound Repair Regen. 2014;22:569–578.
Öhnstedt E, Lofton Tomenius H, Vågesjö E, et al. The discovery and development of topical medicines for wound healing. Expert Opin Drug Discov. 2019;14:485–497.
DOI:https://doi.org/10.1080/17460441.2019.1588879
Teixeira TL, Castilhos P, Rodrigues CC, et al. Experimental evidences that P21 protein controls Trypanosoma cruzi replication and modulates the pathogenesis of infection. Microb Pathog. 2019;135:103618.
DOI:https://doi.org/10.1016/j.micpath.2019.103618
Teixeira TL, Machado FC, Alves Da Silva A, et al. Trypanosoma cruzi P21: A potential novel target for chagasic cardiomyopathy therapy. Sci Rep. 2015;5:1–10.
da Silva CV, Kawashita SY, Probst CM, et al. Characterization of a 21 kDa protein from Trypanosoma cruzi associated with mammalian cell invasion. Microbes Infect. 2009;11:563–570
Bradford M. Snakes of India: The Field Guide. 1976;72:248–254.
Available:http://www.rotoplast.com.co/sistema-septico-domiciliario/
Pinto N de CC, Cassini-Vieira P, Souza-Fagundes EM de, et al. Pereskia aculeata Miller leaves accelerate excisional wound healing in mice. J Ethnopharmacol. 2016; 194:131–136.
DOI:http://dx.doi.org/10.1016/j.jep.2016.09.005
Rasband W. Image J, US. National institutes of health, Bethesda, Maryland, USA; 2011.
Available:http://rsb.info.nih.gov/ij
Available:http://imagej.nih.gov/ij/
De Moura FBR, Justino AB, Ferreira BA, et al. Pro-fibrogenic and Anti-Inflammatory potential of a polyphenol-enriched fraction from annona crassiflora in skin repair. Planta Med. 2019;85:570–577.
Bradley PP, Priebat DA, Christensen RD, et al. Measurement of cutaneous inflammation: Estimation of neutrophil content with an enzyme marker. J Invest Dermatol. 1982;78:206–209.
DOI:http://dx.doi.org/10.1111/1523-1747.ep12506462
Bailey PJ. Sponge implants as models. Methods Enzymol. 1988;162:327–334.
Castanheira LE, Lopes DS, Gimenes SNC, et al. Angiogenenic effects of BpLec, a C-type lectin isolated from Bothrops pauloensis snake venom. Int J Biol Macromol. 2017;102:153–161.
DOI:http://dx.doi.org/10.1016/j.ijbiomac.2017.04.012
Ellis S, Lin EJ, Tartar D. Immunology of wound healing. Curr Dermatol Rep. 2018; 7:350–358.
Taylor KR, Trowbridge JM, Rudisill JA, et al. Hyaluronan fragments stimulate endothelial recognition of injury through TLR4. J Biol Chem. 2004;279:17079–17084.
Willenborg S, Lucas T, Van Loo G, et al. CCR2 recruits an inflammatory macrophage subpopulation critical for angiogenesis in tissue repair. Blood. 2012; 120:613–625.
Rodrigues AA, Clemente TM, dos Santos MA, et al. A recombinant protein based on trypanosoma cruzi P21 enhances phagocytosis. PLoS One. 2012;7:1–9.
Krzyszczyk P, Schloss R, Palmer A, et al. The role of macrophages in acute and chronic wound healing and interventions to promote pro-wound healing phenotypes. Front Physiol. 2018;9:1–22.
Komi DEA, Khomtchouk K, Santa Maria PL. A review of the contribution of mast cells in wound healing: Involved molecular and cellular mechanisms. Clin Rev Allergy Immunol; 2019.
Kalesnikoff J, Galli SJ. New developments in mast cell biology. Nat Immunol. 2008;9:1215–1223
Löffek S, Schilling O, Franzke CW. Series matrix metalloproteinases in lung health and disease“ edited by J. Müller-Quernheim and O”. Eickelberg number 1 in this series: Biological role of matrix metalloproteinases: A critical balance. Eur Respir J. 2011;38:191–208.
Griffiths K, Habiel DM, Jaffar J, et al. Anti-fibrotic effects of CXCR4-targeting i-body AD-114 in Preclinical Models of Pulmonary Fibrosis. Sci Rep. 2018;8:1–15.
DOI:http://dx.doi.org/10.1038/s41598-018-20811-5
Leask A, Abraham DJ. TGF-β signaling and the fibrotic response. FASEB J. 2004;18:816–827
Margadant C, Sonnenberg A. Integrin-TGF-Β crosstalk in fibrosis, cancer and wound healing. EMBO Rep. 2010;11:97–105
Nguyen JK, Austin E, Huang A, et al. The IL-4/IL-13 axis in skin fibrosis and scarring: Mechanistic concepts and therapeutic targets. Arch Dermatol Res; 2019.
DOI: https://doi.org/10.1007/s00403-019-01972-3
Sato T, Liu X, Basma H, et al. IL-4 induces differentiation of human embryonic stem cells into fibrogenic fibroblast-like cells. J Allergy Clin Immunol. 2011;127:1595-1603.e9.
DOI:http://dx.doi.org/10.1016/j.jaci.2011.01.049.
Moens S, Goveia J, Stapor PC, et al. The multifaceted activity of VEGF in angiogenesis- Implications for therapy responses. Cytokine Growth Factor Rev. 2014;25:473–482.
DOI:http://dx.doi.org/10.1016/j.cytogfr.2014.07.009
Duran CL, Howell DW, Dave JM, et al. Molecular regulation of sprouting angiogenesis. Compr Physiol. 2018;8:153–235.
DiPietro LA. Angiogenesis and wound repair: When enough is enough. J Leukoc Biol. 2016;100:979–984.
Guedes-da-Silva FH, Shrestha D, Salles BC, et al. Trypanosoma cruzi antigens induce inflammatory angiogenesis in a mouse subcutaneous sponge model. Microvasc Res. 2015;97:130–136.
DOI:http://dx.doi.org/10.1016/j.mvr.2014.10.007
Teixeira SC, Lopes DS, Gimenes SNC, et al. Mechanistic Insights into the anti-angiogenic activity of trypanosoma cruzi protein 21 and its potential impact on the onset of chagasic cardiomyopathy. Sci Rep. 2017;7:1–14.
Yin H, Chen CY, Liu YW, et al. Synechococcus elongatus PCC7942 secretes extracellular vesicles to accelerate cutaneous wound healing by promoting angiogenesis. Theranostics 2019;9:2678–2693.
Barrientos S, Brem H, Stojadinovic O, et al. Clinical application of growth factors and cytokines in wound healing. Wound Repair Regen. 2014;22:569–578.
Öhnstedt E, Lofton Tomenius H, Vågesjö E, et al. The discovery and development of topical medicines for wound healing. Expert Opin Drug Discov. 2019;14:485–497.
DOI:https://doi.org/10.1080/17460441.2019.1588879
Teixeira TL, Castilhos P, Rodrigues CC, et al. Experimental evidences that P21 protein controls Trypanosoma cruzi replication and modulates the pathogenesis of infection. Microb Pathog. 2019;135:103618.
DOI:https://doi.org/10.1016/j.micpath.2019.103618
Teixeira TL, Machado FC, Alves Da Silva A, et al. Trypanosoma cruzi P21: A potential novel target for chagasic cardiomyopathy therapy. Sci Rep. 2015;5:1–10.
da Silva CV, Kawashita SY, Probst CM, et al. Characterization of a 21 kDa protein from Trypanosoma cruzi associated with mammalian cell invasion. Microbes Infect. 2009;11:563–570
Bradford M. Snakes of India: The Field Guide. 1976;72:248–254.
Available:http://www.rotoplast.com.co/sistema-septico-domiciliario/
Pinto N de CC, Cassini-Vieira P, Souza-Fagundes EM de, et al. Pereskia aculeata Miller leaves accelerate excisional wound healing in mice. J Ethnopharmacol. 2016; 194:131–136.
DOI:http://dx.doi.org/10.1016/j.jep.2016.09.005
Rasband W. Image J, US. National institutes of health, Bethesda, Maryland, USA; 2011.
Available:http://rsb.info.nih.gov/ij
Available:http://imagej.nih.gov/ij/
De Moura FBR, Justino AB, Ferreira BA, et al. Pro-fibrogenic and Anti-Inflammatory potential of a polyphenol-enriched fraction from annona crassiflora in skin repair. Planta Med. 2019;85:570–577.
Bradley PP, Priebat DA, Christensen RD, et al. Measurement of cutaneous inflammation: Estimation of neutrophil content with an enzyme marker. J Invest Dermatol. 1982;78:206–209.
DOI:http://dx.doi.org/10.1111/1523-1747.ep12506462
Bailey PJ. Sponge implants as models. Methods Enzymol. 1988;162:327–334.
Castanheira LE, Lopes DS, Gimenes SNC, et al. Angiogenenic effects of BpLec, a C-type lectin isolated from Bothrops pauloensis snake venom. Int J Biol Macromol. 2017;102:153–161.
DOI:http://dx.doi.org/10.1016/j.ijbiomac.2017.04.012
Ellis S, Lin EJ, Tartar D. Immunology of wound healing. Curr Dermatol Rep. 2018; 7:350–358.
Taylor KR, Trowbridge JM, Rudisill JA, et al. Hyaluronan fragments stimulate endothelial recognition of injury through TLR4. J Biol Chem. 2004;279:17079–17084.
Willenborg S, Lucas T, Van Loo G, et al. CCR2 recruits an inflammatory macrophage subpopulation critical for angiogenesis in tissue repair. Blood. 2012; 120:613–625.
Rodrigues AA, Clemente TM, dos Santos MA, et al. A recombinant protein based on trypanosoma cruzi P21 enhances phagocytosis. PLoS One. 2012;7:1–9.
Krzyszczyk P, Schloss R, Palmer A, et al. The role of macrophages in acute and chronic wound healing and interventions to promote pro-wound healing phenotypes. Front Physiol. 2018;9:1–22.
Komi DEA, Khomtchouk K, Santa Maria PL. A review of the contribution of mast cells in wound healing: Involved molecular and cellular mechanisms. Clin Rev Allergy Immunol; 2019.
Kalesnikoff J, Galli SJ. New developments in mast cell biology. Nat Immunol. 2008;9:1215–1223
Löffek S, Schilling O, Franzke CW. Series matrix metalloproteinases in lung health and disease“ edited by J. Müller-Quernheim and O”. Eickelberg number 1 in this series: Biological role of matrix metalloproteinases: A critical balance. Eur Respir J. 2011;38:191–208.
Griffiths K, Habiel DM, Jaffar J, et al. Anti-fibrotic effects of CXCR4-targeting i-body AD-114 in Preclinical Models of Pulmonary Fibrosis. Sci Rep. 2018;8:1–15.
DOI:http://dx.doi.org/10.1038/s41598-018-20811-5
Leask A, Abraham DJ. TGF-β signaling and the fibrotic response. FASEB J. 2004;18:816–827
Margadant C, Sonnenberg A. Integrin-TGF-Β crosstalk in fibrosis, cancer and wound healing. EMBO Rep. 2010;11:97–105
Nguyen JK, Austin E, Huang A, et al. The IL-4/IL-13 axis in skin fibrosis and scarring: Mechanistic concepts and therapeutic targets. Arch Dermatol Res; 2019.
DOI: https://doi.org/10.1007/s00403-019-01972-3
Sato T, Liu X, Basma H, et al. IL-4 induces differentiation of human embryonic stem cells into fibrogenic fibroblast-like cells. J Allergy Clin Immunol. 2011;127:1595-1603.e9.
DOI:http://dx.doi.org/10.1016/j.jaci.2011.01.049.
Moens S, Goveia J, Stapor PC, et al. The multifaceted activity of VEGF in angiogenesis- Implications for therapy responses. Cytokine Growth Factor Rev. 2014;25:473–482.
DOI:http://dx.doi.org/10.1016/j.cytogfr.2014.07.009
Duran CL, Howell DW, Dave JM, et al. Molecular regulation of sprouting angiogenesis. Compr Physiol. 2018;8:153–235.
DiPietro LA. Angiogenesis and wound repair: When enough is enough. J Leukoc Biol. 2016;100:979–984.
Guedes-da-Silva FH, Shrestha D, Salles BC, et al. Trypanosoma cruzi antigens induce inflammatory angiogenesis in a mouse subcutaneous sponge model. Microvasc Res. 2015;97:130–136.
DOI:http://dx.doi.org/10.1016/j.mvr.2014.10.007
Teixeira SC, Lopes DS, Gimenes SNC, et al. Mechanistic Insights into the anti-angiogenic activity of trypanosoma cruzi protein 21 and its potential impact on the onset of chagasic cardiomyopathy. Sci Rep. 2017;7:1–14.
-
Abstract View: 722 times
PDF Download: 452 times
