Abstract
Background: Despite the continued development of modern medicine, chronic wounds are still a critical issue in clinical treatment, placing a great physiological, psychological, and financial burden on patients. Researchers have investigated many methods to solve this problem, with bioactive peptides gaining increasing attention due to their considerable advantages and diverse functions, as well as low cost, simple storage, and easy transportation.
Methods: In this research, a novel peptide (named OA-FF10) was identified from the skin secretions of the odorous frog species Odorrana andersonii. The sequence of mature OA-FF10 was “FFTTSCRSGC”, which was produced by the post-translational processing of a 61-residue prepropeptide.
Results: Similar to most frog peptides, OA-FF10 showed an intramolecular disulfide bridge at the C-terminus. OA-FF10 demonstrated no antibacterial, antioxidant, hemolytic, or acute toxic activity, but promoted wound healing and proliferation of human keratinocytes (HaCaT) both time- and dose-dependently. Furthermore, while OA-FF10 had no effect on wound healing of Human Skin Fibroblasts (HSF), it did accelerate healing in a full-thickness skin-wound mouse model.
Conclusion: Our research revealed the strong wound-healing activity of OA-FF10 in vivo and in vitro, thus providing a new candidate for the development of novel wound-healing drugs.
Keywords: Odorrana andersonii, wound healing, skin secretions, bioactive peptide, prepropeptide, human keratinocytes.
Graphical Abstract
[1]
Magert, H.J.; Drogemuller, K.; Raghunath, M. Serine proteinase inhibitors in the skin: Role in homeostasis and disease. Curr. Protein Pept. Sci., 2005, 6(3), 241-254.
[2]
Cao, X.; Wang, Y.; Wu, C.; Li, X.; Fu, Z.; Yang, M.; Bian, W.; Wang, S.; Song, Y.; Tang, J.; Yang, X. Cathelicidin-OA1, a novel antioxidant peptide identified from an amphibian, accelerates skin wound healing. Sci. Rep., 2018, 8(1), 943.
[3]
Heng, M.C. Wound healing in adult skin: Aiming for perfect regeneration. Int. J. Dermatol., 2011, 50(9), 1058-1066.
[4]
Moseley, R.; Stewart, J.E.; Stephens, P.; Waddington, R.J.; Thomas, D.W. Extracellular matrix metabolites as potential biomarkers of disease activity in wound fluid: Lessons learned from other inflammatory diseases? Br. J. Dermatol., 2004, 150(3), 401-413.
[5]
Li, X.; Wang, Y.; Zou, Z.; Yang, M.; Wu, C.; Su, Y.; Tang, J.; Yang, X. OM-LV20, a novel peptide from odorous frog skin, accelerates wound healing in vitro and in vivo. Chem. Biol. Drug Des., 2018, 91(1), 126-136.
[6]
Mansour, S.C.; de la Fuente-Nunez, C.; Hancock, R.E. Peptide IDR-1018: Modulating the immune system and targeting bacterial biofilms to treat antibiotic-resistant bacterial infections. J. Pept. Sci., 2015, 21(5), 323-329.
[7]
Hess, T.C. Checklist for factors affecting wound healing. Adv. Skin Wound Care, 2011, 24(4), 192.
[8]
Robson, M.C.; Mustoe, T.A.; Hunt, T.K. The future of recombinant growth factors in wound healing. Am. J. Surg., 1998, 176(2A Suppl), 80S-82S.
[9]
Atalay, M.; Oksala, N.; Lappalainen, J.; Laaksonen, D.E.; Sen, C.K.; Roy, S. Heat shock proteins in diabetes and wound healing. Curr. Protein Pept. Sci., 2009, 10(1), 85-95.
[10]
Hardwicke, J.; Schmaljohann, D.; Boyce, D.; Thomas, D. Epidermal growth factor therapy and wound healing--past, present and future perspectives. Surgeon, 2008, 6(3), 172-177.
[11]
Lian, N.; Li, T. Growth factor pathways in hypertrophic scars: Molecular pathogenesis and therapeutic implications. Biomed. Pharmacother., 2016, 84, 42-50.
[13]
Wang, Y.; Zhang, Y.; Lee, W.H.; Yang, X.; Zhang, Y. Novel peptides from skins of amphibians showed broad‐spectrum antimicrobial activities. Chem. Biol. Drug Des., 2016, 87(3), 419-424.
[14]
Musale, V.; Casciaro, B.; Mangoni, M.L.; Abdel-Wahab, Y.H.A.; Flatt, P.R.; Michael Conlon, J. Assessment of the potential of temporin peptides from the frog Rana temporaria (Ranidae) as anti-diabetic agents. J. Pept. Sci., 2018, 24, (2), (in press).
[15]
Fosgerau, K.; Hoffmann, T. Peptide therapeutics: Current status and future directions. Drug Discov. Today, 2015, 20(1), 122-128.
[16]
Yang, X.; Wang, Y.; Zhang, Y.; Lee, W.H.; Zhang, Y. Rich diversity and potency of skin antioxidant peptides revealed a novel molecular basis for high-altitude adaptation of amphibians. Sci. Rep., 2016, 6, 19866.
[17]
Guimaraes, A.B.; Costa, F.J.; Pires, O.R.; Fontes, W.; Castro, M.S. The amazing world of peptide engineering: The example of antimicrobial peptides from frogs and their analogues. Protein Pept. Lett., 2016, 23(8), 722-737.
[18]
Wu, Y.; Li, R.; Ma, J.; Zhou, M.; Wang, L.; McClure, T.I.; Cai, J.; Chen, T.; Shaw, C. Ranachensinin: A novel aliphatic tachykinin from the skin secretion of the Chinese brown frog, Rana chensinensis. Protein Pept. Lett., 2013, 20(11), 1217-1224.
[19]
Barra, D.; Simmaco, M. Amphibian skin: A promising resource for antimicrobial peptides. Trends Biotechnol., 1995, 13(6), 205-209.
[20]
Bertolotti, E.; Malagoli, D.; Franchini, A. Skin wound healing in different aged Xenopus laevis. J. Morphol., 2013, 274(8), 956-964.
[21]
Yokoyama, H.; Maruoka, T.; Aruga, A.; Amano, T.; Ohgo, S.; Shiroishi, T.; Tamura, K. Prx-1 expression in Xenopus laevis scarless skin-wound healing and its resemblance to epimorphic regeneration. J. Invest. Dermatol., 2011, 131(12), 2477-2485.
[22]
Tang, J.; Liu, H.; Gao, C.; Mu, L.; Yang, S.; Rong, M.; Zhang, Z.; Liu, J.; Ding, Q.; Lai, R. A small peptide with potential ability to promote wound healing. PLoS One, 2014, 9(3), e92082.
[23]
Mu, L.; Tang, J.; Liu, H.; Shen, C.; Rong, M.; Zhang, Z.; Lai, R. A potential wound-healing-promoting peptide from salamander skin. FASEB J., 2014, 28(9), 3919-3929.
[24]
Di Grazia, A.; Cappiello, F.; Imanishi, A.; Mastrofrancesco, A.; Picardo, M.; Paus, R.; Mangoni, M.L. The frog skin-derived antimicrobial peptide esculentin-1a(1-21)NH2 promotes the migration of human HaCaT keratinocytes in an EGF Receptor-dependent manner: A novel Promoter of human skin wound healing? PLoS One, 2015, 10(6), e0128663.
[25]
Yang, X.; Lee, W.H.; Zhang, Y. Extremely abundant antimicrobial peptides existed in the skins of nine kinds of Chinese odorous frogs. J. Proteome Res., 2012, 11(1), 306-319.
[26]
Liu, H.; Mu, L.; Tang, J.; Shen, C.; Gao, C.; Rong, M.; Zhang, Z.; Liu, J.; Wu, X.; Yu, H.; Lai, R. A potential wound healing-promoting peptide from frog skin. Int. J. Biochem. Cell Biol., 2014, 49, 32-41.
[27]
Conlon, J.M.; Kolodziejek, J.; Nowotny, N. Antimicrobial peptides from ranid frogs: Taxonomic and phylogenetic markers and a potential source of new therapeutic agents. Biochim. Biophys. Acta, 2004, 1696(1), 1-14.
[28]
Duda, T.F. Jr.; Vanhoye, D.; Nicolas, P. Roles of diversifying selection and coordinated evolution in the evolution of amphibian antimicrobial peptides. Mol. Biol. Evol., 2002, 19(6), 858-864.
[29]
Shang, W.; Yang, X.; Ju, X.; Xie, Y.; Zhang, Y.; Lee, W.H. Characterization of an insulinotropic peptide from skin secretions of Odorrana andersonii. J. Pept. Sci., 2017, 23(9), 707-715.
[30]
Chen, Z.; Yang, X.; Liu, Z.; Zeng, L.; Lee, W.; Zhang, Y. Two novel families of antimicrobial peptides from skin secretions of the Chinese torrent frog, Amolops jingdongensis. Biochimie, 2012, 94(2), 328-334.
[31]
Zhou, M.; Chen, T.; Walker, B.; Shaw, C. Lividins: novel antimicrobial peptide homologs from the skin secretion of the Chinese Large Odorous frog, Rana(Odorrana) livida. Identification by “shotgun” cDNA cloning and sequence analysis. Peptides, 2006, 27(9), 2118-2123.
[32]
Wang, M.; Wang, Y.; Wang, A.; Song, Y.; Ma, D.; Yang, H.; Ma, Y.; Lai, R. Five novel antimicrobial peptides from skin secretions of the frog, Amolops loloensis. Comp. Biochem. Physiol. B Biochem. Mol. Biol., 2010, 155(1), 72-76.
[33]
Conlon, J.M. Structural diversity and species distribution of host-defense peptides in frog skin secretions. Cell. Mol. Life Sci., 2011, 68(13), 2303-2315.
[34]
Wang, Y.; Zhang, Y.; Lee, W.H.; Yang, X.; Zhang, Y. Novel peptides from skins of amphibians showed broad-spectrum antimicrobial activities. Chem. Biol. Drug Des., 2016, 87(3), 419-424.
[35]
Lai, R.; Zheng, Y.T.; Shen, J.H.; Liu, G.J.; Liu, H.; Lee, W.H.; Tang, S.Z.; Zhang, Y. Antimicrobial peptides from skin secretions of Chinese red belly toad Bombina maxima. Peptides, 2002, 23(3), 427-435.
[36]
Lai, R.; Liu, Hui .; H, Lee. W.; Zhang, Y. A novel bradykinin-related peptide from skin secretions of toad Bombina maxima and its precursor containing six identical copies of the final product. Biochem. Biophys. Res. Commun., 2001, 286(2), 259-263.
[37]
Conlon, J.M.; Aronsson, U. Multiple bradykinin-related peptides from the skin of the frog, Rana temporaria. Peptides, 1997, 18(3), 361-365.
[38]
Simmaco, M.; De Biase, D.; Severini, C.; Aita, M.; Erspamer, G.F.; Barra, D.; Bossa, F. Purification and characterization of bioactive peptides from skin extracts of Rana esculenta. Biochim. Biophys. Acta, 1990, 1033(3), 318-323.
Related Journals
Current Protein & Peptide Science
Related Books
Frontiers in Protein and Peptide Sciences
Article Metrics
47
11