Skip to main content
SpringerLink
Log in

Oligomeric Procyanidins (OPCs) Inhibit Procollagen Type I Secretion of Fibroblasts

  • Original Article
  • Published:
Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Wound healing is composed of a complex process that requires harmonies of various cell populations where fibroblasts play the main role. Oligomeric procyanidins (OPC) are main components of grape (Vitis vinifera) seed extracts, and recent studies showed OPC’s effects on inflammation, cell migration, and proliferation. We investigated the effect of OPC on fibroblasts to regulate wound healing process. Human dermal fibroblast known as Hs27 cells were treated with various concentrations of OPC (0, 2.5, 5, 10, and 20 μg/μl). Cell cytotoxicity was evaluated by the Cell Counting Kit assay, and the expression levels of secreted procollagen were analyzed. Procollagen levels in OPC treated cells exposed to transforming growth factor beta 1 (TGF-β1) or ascorbic acid were evaluated using Western blot and immunocytochemistry. Relative mRNA expressions of procollagen, molecular chaperone such as HSP47, P4H were determined by real-time PCR in OPC treated cells. OPC showed no cytotoxicity on Hs27 cells at every concentration but inhibited procollagen secretion in a dose-dependent manner. The inhibitory effect also appeared under TGF-β1 induced collagen overproduction. Immunocytochemistry showed that higher levels of intracytoplasmic procollagen were accumulated in TGF-β1 treatment group, whereas ascorbic acid induced a release of accumulated procollagen under OPC treatment. The mRNA expressions of procollagen, molecular chaperone were not affected by OPC, but procollagen level was increased when exposed to TGF-β1. OPC inhibits procollagen secretion from fibroblasts with no effects on cell proliferations even under the environment of TGF-β1-induced collagen overproduction. OPC could regulate the diseases and symptoms of abnormal overabundant collagen production.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Hopkinson I, Leaper DJ, McKay IA. Review of classic research: control of scarring. J Wound Care. 1995;4:430–3.

    Article  Google Scholar 

  2. Chau D, Mancoll JS, Lee S, Zhao J, Phillips LG, Gittes GK, et al. Tamoxifen downregulates TGF-beta production in keloid fibroblasts. Ann Plast Surg. 1998;40:490–3.

    Article  CAS  PubMed  Google Scholar 

  3. Zhang K, Garner W, Cohen L, Rodriguez J, Phan S. Increased types I and III collagen and transforming growth factor-beta 1 mRNA and protein in hypertrophic burn scar. J Invest Dermatol. 1995;104:750–4.

    Article  CAS  PubMed  Google Scholar 

  4. Sudjaroen Y, Haubner R, Wurtele G, Hull WE, Erben G, Spiegelhalder B, et al. Isolation and structure elucidation of phenolic antioxidants from Tamarind (Tamarindus indica L.) seeds and pericarp. Food Chem Toxicol. 2005;43:1673–82.

    Article  CAS  PubMed  Google Scholar 

  5. Ling ZQ, Xie BJ, Yang EL. Isolation, characterization, and determination of antioxidative activity of oligomeric procyanidins from the seedpod of Nelumbo nucifera Gaertn. J Agric Food Chem. 2005;53:2441–5.

    Article  CAS  PubMed  Google Scholar 

  6. Joseph GS, Jayaprakasha GK, Selvi AT, Jena BS, Sakariah KK. Antiaflatoxigenic and antioxidant activities of Garcinia extracts. Int J Food Microbiol. 2005;101:153–60.

    Article  CAS  PubMed  Google Scholar 

  7. Kim Y, Choi Y, Ham H, Jeong HS, Lee J. Antioxidant and cytoprotective effects of oligomeric and polymeric procyanidin fractions from defatted grape seed in PC12 cells. J Med Food. 2012;15:490–4.

    Article  CAS  PubMed  Google Scholar 

  8. Terra X, Valls J, Vitrac X, Merrillon JM, Arola L, Ardevol A, et al. Grape-seed procyanidins act as antiinflammatory agents in endotoxin-stimulated RAW 264.7 macrophages by inhibiting NFkB signaling pathway. J Agric Food Chem. 2007;55:4357–65.

    Article  CAS  PubMed  Google Scholar 

  9. Garcia-Conesa MT, Tribolo S, Guyot S, Tomas-Barberan FA, Kroon PA. Oligomeric procyanidins inhibit cell migration and modulate the expression of migration and proliferation associated genes in human umbilical vascular endothelial cells. Mol Nutr Food Res. 2009;53:266–76.

    Article  CAS  PubMed  Google Scholar 

  10. Berti F, Manfredi B, Mantegazza P, Rossoni G. Procyanidins from Vitis vinifera seeds display cardioprotection in an experimental model of ischemia-reperfusion damage. Drugs Exp Clin Res. 2003;29:207–16.

    CAS  PubMed  Google Scholar 

  11. Oak MH, El Bedoui J, Schini-Kerth VB. Antiangiogenic properties of natural polyphenols from red wine and green tea. J Nutr Biochem. 2005;16:1–8.

    Article  CAS  PubMed  Google Scholar 

  12. Ishiyama M, Tominaga H, Shiga M, Sasamoto K, Ohkura Y, Ueno K. A combined assay of cell viability and in vitro cytotoxicity with a highly water-soluble tetrazolium salt, neutral red and crystal violet. Biol Pharm Bull. 1996;19:1518–20.

    Article  CAS  PubMed  Google Scholar 

  13. Smith RS, Smith TJ, Blieden TM, Phipps RP. Fibroblasts as sentinel cells. Synthesis of chemokines and regulation of inflammation. Am J Pathol. 1997;151:317–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Zhang HJ, Ji BP, Chen G, Zhou F, Luo YC, Yu HQ, et al. A combination of grape seed-derived procyanidins and gypenosides alleviates insulin resistance in mice and HepG2 cells. J Food Sci. 2009;74:H1–7.

    Article  CAS  PubMed  Google Scholar 

  15. Varga J, Rosenbloom J, Jimenez SA. Transforming growth factor beta (TGF beta) causes a persistent increase in steady-state amounts of type I and type III collagen and fibronectin mRNAs in normal human dermal fibroblasts. Biochem. 1987;247:597–604.

    Article  CAS  Google Scholar 

  16. Younai S, Nichter LS, Wellisz T, Reinisch J, Nimni ME, Tuan TL. Modulation of collagen synthesis by transforming growth factor-beta in keloid and hypertrophic scar fibroblasts. Ann Plast Surg. 1994;33:148–51.

    Article  CAS  PubMed  Google Scholar 

  17. Murad S, Grove D, Lindberg KA, Reynolds G, Sivarajah A, Pinnell SR. Regulation of collagen synthesis by ascorbic acid. Proc Natl Acad Sci USA. 1981;78:2879–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Berg RA, Prockop DJ. The thermal transition of a non-hydroxylated form of collagen. Evidence for a role for hydroxyproline in stabilizing the triple-helix of collagen. Biochem Biophys Res Commun. 1973;52:115–20.

    Article  CAS  PubMed  Google Scholar 

  19. Tasab M, Batten MR, Bulleid NJ. Hsp47: a molecular chaperone that interacts with and stabilizes correctly-folded procollagen. EMBO J. 2000;19:2204–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hirayoshi K, Kudo H, Takechi H, Nakai A, Iwamatsu A, Yamada KM, et al. HSP47: a tissue-specific, transformation-sensitive, collagen-binding heat shock protein of chicken embryo fibroblasts. Mol Cell Biol. 1991;11:4036–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kivirikko KI, Myllyharju J. Prolyl 4-hydroxylases and their protein disulfide isomerase subunit. Matrix Biol. 1998;16:357–68.

    Article  CAS  PubMed  Google Scholar 

  22. Lamande SR, Bateman JF. Procollagen folding and assembly: the role of endoplasmic reticulum enzymes and molecular chaperones. Semin Cell Dev Biol. 1999;10:455–64.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This research was supported by a Grant through the Disaster and Safety Management Institute (MPSS-CG-2016-02), Center for Research and Development of Police science and Technology and Korean National Police Agency (PA-H000001), Ministry of Health & Welfare (HI14C2310), and the Korea Research Institute of Bioscience and Biotechnology (KGM4891511), Republic of Korea.

Author information

Author notes

    Authors and Affiliations

    1. Department of Plastic and Reconstructive Surgery, College of Medicine, Seoul National University, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Korea

      Byung Jun Kim, Byeong Kyu Kim, Soo Jin Park, Min Kyung Kim & La Mee Choi

    2. Faceplus Aesthetic Clinic, 856 Eonju-ro, Gangnam-gu, Seoul, 06017, Korea

      Jung-Keun Park

    3. Hana Academy Seoul, 535 Yeonseo-ro, Eunpyeong-gu, Seoul, 03305, Korea

      Chang-won Lee

    4. Department of Internal Medicine, School of Medicine, Yeungnam University, 170 Hyeonchung-ro, Nam-gu, Daegu, 42415, Korea

      Ji An Hur

    5. Department of Internal Medicine, Keimyung University Dongsan Medical Center, 56 Dalseong-ro, Daegu, 41931, Korea

      Sang Hyon Kim

    6. Department of Rehabilitation Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon, 35015, Korea

      Jaewon Beom

    7. Department of Biomedical Engineering, College of Medicine, Seoul National University, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Korea

      Jaewon Beom

    8. Department of Rehabilitation Medicine, Dankook University Hospital, 119 Dandae-ro, Cheonan, 31116, Korea

      Jung Yoon Kim

    9. Department of Rehabilitation Medicine, College of Medicine, Seoul National University, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Korea

      Byung-Mo Oh

    10. Department of Plastic and Reconstructive Surgery, Institute of Human Environment Interface Biology, College of Medicine, Seoul National University, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Korea

      Tae Hyun Choi & Sukwha Kim

    11. Department of Plastic and Reconstructive Surgery, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea

      Tae Hyun Choi

    Authors
    1. Byung Jun Kim
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Jung-Keun Park
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Byeong Kyu Kim
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Soo Jin Park
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Min Kyung Kim
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Chang-won Lee
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. La Mee Choi
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Ji An Hur
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Sang Hyon Kim
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Jaewon Beom
      View author publications

      You can also search for this author in PubMed Google Scholar

    11. Jung Yoon Kim
      View author publications

      You can also search for this author in PubMed Google Scholar

    12. Byung-Mo Oh
      View author publications

      You can also search for this author in PubMed Google Scholar

    13. Tae Hyun Choi
      View author publications

      You can also search for this author in PubMed Google Scholar

    14. Sukwha Kim
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Tae Hyun Choi.

    Ethics declarations

    Conflict of interest

    The authors have no financial conflicts of interest.

    Ethical statement

    This paper does not include any ethical issues for human and animal rights.

    Additional information

    Byung Jun Kim and Jung-Keun Park contributed equally to this paper as first authors.

    Tae Hyun Choi and Sukwha Kim contributed equally to this paper as corresponding authors.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Kim, B.J., Park, JK., Kim, B.K. et al. Oligomeric Procyanidins (OPCs) Inhibit Procollagen Type I Secretion of Fibroblasts. Tissue Eng Regen Med 14, 297–306 (2017). https://doi.org/10.1007/s13770-017-0038-1

    Download citation

    • Received:

    • Revised:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s13770-017-0038-1

    Keywords

    Search

    Navigation