Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2016, vol. 25, nr 2, March-April, p. 227–235

doi: 10.17219/acem/36361

Publication type: original article

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

Identification of Small Peptides of Acidic Collagen Extracts from Silver Carp Skin and Their Therapeutic Relevance

Diana Wojtkowiak1,B,C,D, Andrzej F. Frydrychowski1,A,E, Jakub Hadzik2,D, Marzena Dominiak2,E,F

1 Institute of Human Physiology, Faculty of Health Sciences, Medical University of Gdańsk, Poland

2 Department of Oral Surgery, Wroclaw Medical University, Poland


Background. Low-temperature techniques that prevent protein denaturation are being used to extract collagen from fish skin for cosmetic purposes. These extracts contain collagen with its triple helix structure preserved, as well as a number of other proteins.
Objectives. The aim of the study was to investigate collagen extracts from the skin of silver carp for the presence of small-molecule peptides.
Material and Methods. Liquid chromatography-mass spectrometry (HPLC-MS) was performed to analyze collagen extracts from silver carp skin for the presence of small-molecule peptides.
Results. A large number of different peptides were detected in the silver carp skin collagen extracts analyzed. Among the smaller peptides, the most abundant were those of 7–29 aminoacids originating from the following proteins: collagen Iα1, collagen Iα2, collagen Iα3, collagen VIα3, decorin, lumican, histone H2A, histone H2B and histone H4.
Conclusion. The study demonstrated that, in addition to high-molecular-weight collagen proteins, acidic collagen extracts acquired from the skin of silver carp at temperatures up to 16°C also contain considerable amounts of small 7–29 amino-acid peptides. The application of these peptides could therefore be expected to result in beneficial clinical effects in patients in need of reconstructive treatment.

Key words

collagen, histones, matrikines, HPLC-MS/MS, silver carp skin peptides

References (60)

  1. Benson HA, Namjoshi S: Proteins and peptides: Strategies for delivery to and across the skin. J Pharm Sci 2008, 97, 3591–3610.
  2. Burget A, Nathan P, Holder IP, Macmillan BG: The effect of a collagen dressing on contaminated surgical wounds in rats. Langenbecks Arch Chir 1976, 343, 69–73.
  3. Purna SK, Babu M: Collagen based dressing – a review. Burns 2000, 26, 54–62.
  4. Fleck CA, Simman R: Modern collagen wound dressing: function and purpose. J Am Coll Certif Wound Spec 2010, 2, 50–54.
  5. Bello TR: Practical treatment of body and open leg wounds of horses with bovine collagen, bisynthetic wound dressing and cyanoacrylate. J Equine Vet Sci 2002, 22, 157–164.
  6. Elgharably H, Ganesh K, Dickerson J, Khanna S, Abas M, Ghatak PD, Dixit S, Bergdall V, Roy S, Sen CK: A modified collagen gel dressing promotes angiogenesis in a preclinical swine model of chronic ischemic wounds. Wound Repair Regen 2014, 22, 720–729.
  7. Frydrychowski AF: Pilot study of collagen gel wound treatment on patients with varicose leg ulcers (results not published).
  8. Moskowitz RW: Role of collagen hydrolysate in bone and joint disease. Semin Arthritis Rheum 2000, 30, 87–99.
  9. Ausar SF, Beltramo DM, Castagna LF, Quintana S, Silvera E, Kalayan G, Revigliono M, Landa CA, Bianco ID: Treatment of rheumatoid arthritis by oral administration of bovine tracheal type II collagen. Rheumatol Int 2001, 20, 138–144.
  10. Wu J, Fujioka M, Sugimoto K, Mu G, Ishimi Y: Assessment of effectiveness of oral administration of collagen peptide on bone metabolism in growing and mature rats. J Bone Miner Metab 2004, 22, 547–553.
  11. Nomura Y, Oohashi K, Watanabe M, Kasugai S: Increase in bone mineral density through oral administration of shark gelatin to ovariectomized rats. Nutrition 2005, 21, 1120–1126.
  12. Guillerminet F, Beaupied H, Fabien-Soule V, Tome D, Benhamou CL, Roux C, Blais A: Hydrolyzed collagen improves bone metabolism and biomechanical parameters in ovariectomized mice: An in vitro and in vivo study. Bone 2010, 46, 827–834.
  13. Park KS, Park MJ, Cho, ML, Kwok SK Ju JH, Ko HJ, Park SH, Kim HY: Type II collagen oral tolerance; mechanism and role in collagen-induced arthritis and rheumatoid arthritis. Mod Rheumatol 2009, 19, 581–589.
  14. Ju JH, Cho ML, Jhun JY, Park MJ, Oh HJ, Min SY, Cho YG, Hwang SY, Kwok SK, Seo SH, Yoon CH, Park SH, Kim HY: Oral administration of type-II collagen suppresses IL-17-associated RANKL expression of CD4+ T cells in collagen-induced arthritis. Immunol Lett 2008, 117, 16–25.
  15. Zagne V: A new view concerning the effects of collagen hydrolysate intake on skin properties. Arch Dermatol Res 2008, 300, 479–483.
  16. Maquart FX, Pasco S, Ramont L, Hornebeck W, Monboisse JC: An introduction to matrikines: extracellular matrix-derived peptides which regulate cell activity. Implication in tumor invasion. Crit Rev Oncol Hematol 2004, 49, 199–202.
  17. Matheson S, Larjava H, Hakkinen L: Distinctive localization and function for lumican, fibromodulin and decorin to regulate collagen fibril organization in periodontal tissues. J Periodontal Res 2005, 40, 312–324.
  18. Ilic MZ, Carter P, Tyndall A, Dudhia J, Handley CJ: Proteoglycans and catabolic products of proteoglycans present in ligament. Biochem J 2005, 385, 381–388.
  19. Davies JE, Tang X, Denning JW, Archibald SJ, Davies SJ: Decorin suppresses neurocan, brevican, phosphacan and NG2 expression and promotes axon growth across adult rat spinal cord injuries. Eur J Neurosci 2004, 19, 1226–1242.
  20. Minor K, Tang X, Kahrilas G, Archibald SJ, Davies JE, Davies SJ: Decorin promotes robust growth on inhibitory CSPGs and myelin via a direct effect on neurons. Neurobiol 2008, Dis 32, 88–95.
  21. Kolb M, Margetts PJ, Sime PJ, Gauldie J: Proteoglycans decorin and biglycan differentially modulate TGF-betamediated fibrotic responses in the lung. Am J Physiol Lung Cell Mol Physiol 2001, 280, 1327–1334.
  22. Weis SM, Zimmerman SD, Shah M, Covell JW, Omens JH, Ross J, Jr Dalton N, JonesY, Reed CC, Iozzo RV, McCulloch AD: A role for decorin in the remodeling of myocardial infarction. Matrix Biol 2005, 24, 313–324.
  23. Xaus J, Comalada M, Cardo M, Valledor AF, Celada A: Decorin inhibits macrophage colony-stimulating factor proliferation of macrophages and enhances cell survival through induction of p27(Kip1) and p21(Waf1). Blood 2001, 98, 2124–2133.
  24. Stewart JE, Wheatley DN, Holmes JD, Muir IF: Purification and identification of a human dermal extract component inhibitory to fibroblast proliferation. Cell Biol Int 2001, 25, 607–612.
  25. Wheatley DN, Graham E, McMaster RS, Muir IF, Holmes JD, Davies M: Recovery of the Decorin-Enriched Fraction, Extract (D), From Human Skin: An Accelerated Protocol. J Biomed Biotechnol 2004, 2004, 211–218.
  26. Zhang Z, Li XJ, Liu Y, Zhang X, Li YY, Xu WS: Recombinant human decorin inhibits cell proliferation and downregulates TGF-beta1 production in hypertrophic scar fibroblasts. Burns 2007, 33, 634–641.
  27. Reed CC, Waterhouse A, Kirby S, Kay P, Owens RT, McQuillan DJ, Iozzo RV: Decorin prevents metastatic spreading of breast cancer. Oncogene 2005, 24, 1104–1110.
  28. Tralhao JG, Schaefer L, Micegova M, Evaristo C, Schonherr E, Kayal S, Veiga-Fernandes H, Danel C, Iozzo RV, Kresse H, Lemarchand P: In vivo selective and distant killing of cancer cells using adenovirus-mediated decorin gene transfer. FASEB J 2003, 17, 464–466.
  29. Stander M, Naumann U, Dumitrescu L, Heneka M, Loschmann P, Gulbins E, Dichgans J, Weller M: Decorin gene transfer-mediated suppression of TGF-beta synthesis abrogates experimental malignant glioma growth in vivo. Gene Ther 1998, 5, 1187–1194.
  30. Santra M, Reed CC, Iozzo RV: Decorin binds to a narrow region of the epidermal growth factor (EGF) receptor, partially overlapping but distinct from the EGF-binding epitope. J Biol Chem 2002, 277, 35671–35681.
  31. Grant DS, Yenisey C, Rose RW, Tootell M, Santra M, Iozzo RV: Decorin suppresses tumor cell-mediated angiogenesis. Oncogene 2002, 21, 4765–4777.
  32. Sulochana KN, Fan H, Jois S, Subramanian V, Sun F, Kini RM, Ge R: Peptides derived from human decorin leucine-rich repeat 5 inhibit angiogenesis. J Biol Chem 2005, 280, 27935–27948.
  33. Fan H, Sulochana KN, Chong YS, Ge R: Decorin derived antiangiogenic peptide LRR5 inhibits endothelial cell migration by interfering with VEGF-stimulated NO release. IJBCB 2008, 40, 2120–2128.
  34. Chakravarti S, Stallings RL, SundarRaj N, Cornuet PK, Hassell JR: Primary structure of human lumican (keratan sulfate proteoglycan) and localization of the gene (LUM) to chromosome 12q21.3-q22. Genomics 1995, 27, 481–488.
  35. Vij N, Roberts L, Joyce S, Chakravarti S: Lumican suppresses cell proliferation and aids Fas-Fas ligand mediated apoptosis: Implications in the cornea. Exp Eye Res 2004, 78, 957–971.
  36. Vuillermoz B, Khoruzhenko A, D’Onofrio MF, Ramont L, Venteo L, Perreau C, Antonicelli F, Maquart FX, Wegrowski Y: The small leucine-rich proteoglycan lumican inhibits melanoma progression. Exp Cell Res 2009, 296, 294–306.
  37. Zeltz C, Brezillon S, Perreau C, Ramont L, Maquart FX, Wegrowski Y: Lumcorin: A leucine-rich repeat 9-derived peptide from human lumican inhibiting melanoma cell migration. FEBS Lett 2009, 583, 3027–3032.
  38. Brezillon S, Radwanska A, Zelts C, Malkowski A, Ploton D, Bobichon H, Perreau C, Malicka-Blaszkiewicz M, Maquart FX, Wegrowski Y: Lumican core protein inhibits melanoma cell migration via alterations of focal adhesion complexes. Cancer Lett 2009, 283, 92–100.
  39. Birkemo GA, Luders T, Andersen O, Nes IF, Nissen-Meyer J: Hipposin, a histone-derived antimicrobial peptide in Atlantic halibut (Hippoglossus hippoglossus L.). Biochim Biophys Acta 2003, 1646, 207–215.
  40. Birkemo GA, Mantzilas D, Luders T, Nes IF, Nissen-Meyer J: Identification and structural analysis of the antimicrobial domain in hipposin, a 51-mer antimicrobial peptide isolated from Atlantic halibut. Biochim Biophys Acta 2004, 1699, 221–227.
  41. Park CB, Kim MS, Kim SC: A novel antimicrobial peptide from Bufo bufo gargarizans. Biochem Biophys Res Commun 1996, 218, 408–413.
  42. Park CB, Yi KS, Matsuzaki K, Kim MS, Kim SC: Structure-activity analysis of buforin II, a histone H2A-derived antimicrobial peptide: the proline hinge is responsible for the cell-penetrating ability of buforin II. Proc Natl Acad Sci U S A 2000, 97, 8245–8250.
  43. Park CB, Kim HS, Kim SC: Mechanism of action of the antimicrobial peptide buforin II: buforin II kills microorganisms by penetrating the cell membrane and inhibiting cellular functions. Biochem Biophys Res Commun 1998, 244, 253–257.
  44. Park IY, Park CB, Kim MS, Kim SC: Parasin I, an antimicrobial peptide derived from histone H2A in the catfish, Parasilurus asotus. FEBS Lett 1998, 437, 258–262.
  45. Cho JH, Park IY, Kim HS, Lee WT, Kim MS, Kim SC: Cathepsin D produces antimicrobial peptide parasin I from histone H2A in the skin mucosa of fish. FASEB J 2002, 16, 429–431.
  46. Cho JH, Park IY, Kim MS, Kim SC: Matrix metalloproteinase 2 is involved in the regulation of the antimicrobial peptide parasin I production in catfish skin mucosa. FEBS Lett 2002, 531, 459–463.
  47. Kawasaki H, Isaacson T, Iwamuro S, Conlon JM: A protein with antimicrobial activity in the skin of Schlegel’s green tree frog Rhacophorus schlegelii (Rhacophoridae) identified as histone H2B. Biochem Biophys Res Commun 2003, 312, 1082–1086.
  48. Tollin M, Bergman P, Svenberg T, Jornvall H, Gudmundsson GH, Agerberth B: Antimicrobial peptides in the first line defence of human colon mucosa. Peptides 2003, 24, 523–530.
  49. Brown OA, Sosa YE, Goya RG: Thyrotropin-releasing activity of histone H2A, H2B and peptide MB35. Peptides 1997, 18, 1315–1319.
  50. Chu AJ, Chen BM, Lin H, Beydoun S: Antimicrobial peptide buforin I inhibits tissue factor-initiated coagulation. Arch Biochem Biophys 2001, 392, 3–7.
  51. Labat-Robert J: Age-dependent remodeling of connective tissue: role of fibronectin and laminin. Pathol Biol (Paris) 2003, 51, 563–568.
  52. Maquart FX, Pasco S, Ramont L, Hornebeck W, Monboisse JC: An introduction to matrikines: extracellular matrix-derived peptides which regulate cell activity. Implication in tumor invasion. Crit Rev Oncol Hematol 2004, 49, 199–202.
  53. Pasco S, Ramont L, Maquart FX, Monboisse JC: Control of melanoma progression by various matrikines from basement membrane macromolecules. Crit Rev Oncol Hematol 2004, 49, 221–233.
  54. Duca L, Floquet N, Alix AJ, Haye B, Debelle L: Elastin as a matrikine. Crit Rev Oncol Hematol 2004, 49, 235–244.
  55. Bellon G, Martiny L, Robinet A: Matrix metalloproteinases and matrikines in angiogenesis. Crit Rev Oncol Hematol 2004, 49, 203–220.
  56. Maquart FX, Bellon G, Pasco S, Monboisse JC: Matrikines in the regulation of extracellular matrix degradation. Biochimie 2005, 87, 353–360.
  57. Tran KT, Lamb P, Deng JS: Matrikines and matricryptins: Implications for cutaneous cancers and skin repair. J Dermatol Sci 2005, 40, 11–20.
  58. Sulochana KN, Fan H, Jois S, Subramanian V, Sun F, Kini RM, Ge R: Peptides derived from human decorin leucine-rich repeat 5 inhibit angiogenesis. J Biol Chem 2005, 280, 27935–27948. (Epub 2005, May 27).
  59. Karagiannis ED, Popel AS: Identification of novel short peptides derived from the alpha 4, alpha 5, and alpha 6 fibrils of type IV collagen with anti-angiogenic properties. Biochem Biophys Res Commun 2007, 354, 434–439. (Epub 2007, Jan 16).
  60. Zeltz C, Brézillon S, Perreau C, Ramont L, Maquart FX, Wegrowski Y: Lumcorin: a leucine-rich repeat 9-derived peptide from human lumican inhibiting melanoma cell migration. FEBS Lett 2009, 583, 3027–3032. DOI: 10.1016/j. febslet.2009.08.012. (Epub 2009, Aug 15).