Skip to main content

Advertisement

SpringerLink
Log in

Erythroid differentiation regulator 1 (Erdr1) enhances wound healing through collagen synthesis in acne skin

  • Original Paper
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

Abstract

Acne is a chronic skin disease of the pilosebaceous unit resulting from Propionibacterium acnes (P. acnes), a commensal microorganism. Although numerous therapies are available for acne, there is still a need for the development of effective therapies. Erythroid differentiation regulator 1 (Erdr1) has been suggested to be beneficial during inflammatory skin diseases. In the current study, we first showed that Erdr1 expression level was lower in inflammatory acne skin compared to the normal skin, suggesting that Erdr1 was negatively regulated in acne skin. To evaluate the effect of Erdr1 further, Erdr1 was injected subcutaneously in the acne mouse model. Results revealed that the necrotic lesions by inflamed acne were dramatically decreased and collagen synthesis and fibroblasts activation were induced by Erdr1. In addition, Erdr1 reduced the infiltration of inflammatory cells in vivo and accelerated collagen production in P. acnes-treated human dermal fibroblasts through TGF-β/Smad signaling. Taken together, Erdr1 enhanced wound healing through acceleration of collagen synthesis and activation of fibroblasts in acne skin, suggesting its potential use for acne improvement.

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

Similar content being viewed by others

References

  1. Bainbridge P (2013) Wound healing and the role of fibroblasts. J Wound Care 22:407–408. https://doi.org/10.12968/jowc.2013.22.8.407

    Article  CAS  PubMed  Google Scholar 

  2. Connolly D, Vu HL, Mariwalla K, Saedi N (2017) Acne scarring-pathogenesis, evaluation, and treatment options. J Clin Aesthet Dermatol 10:12–23

    PubMed  PubMed Central  Google Scholar 

  3. Das F, Bera A, Ghosh-Choudhury N, Abboud HE, Kasinath BS, Choudhury GG (2014) TGFβ-induced deptor suppression recruits mTORC1 and not mTORC2 to enhance collagen I (β2) gene expression. PLoS O ne 9:e109608. https://doi.org/10.1371/journal.pone.0109608

    Article  CAS  Google Scholar 

  4. Dessinioti C, Katsambasa A (2017) Propionibacterium acnes and antimicrobial resistance in acne. Clin Dermatol 35:163–167. https://doi.org/10.1016/j.clindermatol.2016.10.008

    Article  PubMed  Google Scholar 

  5. Ghosh AK, Bhattacharyya S, Lakos G, Chen SJ, Mori J, Varga J (2004) Disruption of transforming growth factor beta signaling and profibrotic responses in normal skin fibroblasts by peroxisome proliferator-activated receptor gamma. Arthritis Rheumatol 50:1305–1318. https://doi.org/10.1002/art.20104

    Article  CAS  Google Scholar 

  6. Hagstrom EL, Patel S, Karimkhani C, Boyers LN, Williams HC, Hay RJ, Weinstock MA, Armstrong AW, Dunnick CA, Margolis DJ, Dellavalle RP (2015) Comparing cutaneous research funded by the US National Institutes of Health (NIH) with the US skin disease burden. J Am Acad Dermatol 73:383–391. https://doi.org/10.1016/j.jaad.2015.04.039

    Article  PubMed  Google Scholar 

  7. Hao J, Ju H, Zhao S, Junaid A, Scammell-La Fleur T, Dixon IM (1999) Elevation of expression of Smads 2, 3, and 4, decorin and TGF-beta in the chronic phase of myocardial infarct scar healing. J Mol Cell Cardiol 31:667–678. https://doi.org/10.1006/jmcc.1998.0902

    Article  CAS  PubMed  Google Scholar 

  8. Houh Y, Kim KE, Park HJ, Cho D (2016) Roles of erythroid differentiation regulator 1 (Erdr1) on inflammatory skin diseases. Int J Mol Sci 17:E2059. https://doi.org/10.3390/ijms17122059

    Article  CAS  PubMed  Google Scholar 

  9. Ishise H, Larson B, Hirata Y, Fujiwara T, Nishimoto S, Kubo T, Matsuda K, Kanazawa S, Sotsuka Y, Fujita K, Kakibuchi M, Kawai K (2015) Hypertrophic scar contracture is mediated by the TRPC3 mechanical force transducer via NFκB activation. Sci Rep 5:11620. https://doi.org/10.1038/srep11620

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Jang YH, Lee KC, Lee SJ, Kim DW, Lee WJ (2015) HR-1 mice: a new inflammatory acne mouse model. Ann Dermatol 27:257–264. https://doi.org/10.5021/ad.2015.27.3.257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Jensen LT (1997) HØst NB Collagen: scaffold for repair or execution. Cardiovasc Res 33:535–539

    Article  CAS  Google Scholar 

  12. Jeremy AH, Holland DB, Roberts SG, Thomson KF, Cunliffe WJ (2003) Inflammatory events are involved in acne lesion initiation. J Investig Dermatol 121:20–27. https://doi.org/10.1046/j.1523-1747.2003.12321.x

    Article  CAS  PubMed  Google Scholar 

  13. Jung MK, Park Y, Song SB, Cheon SY, Park S, Houh Y, Ha S, Kim HJ, Park JM, Kim TS, Lee WJ, Cho BJ, Bang SI, Park H, Cho D (2011) Erythroid differentiation regulator 1, an interleukin 18-regulated gene, acts as a metastasis suppressor in melanoma. J Investig Dermatol 131:2096–2104. https://doi.org/10.1038/jid.2011.170

    Article  CAS  PubMed  Google Scholar 

  14. Kelhala HL, Palatsi R, Fyhrquist N, Lehtimaki S, Vayrynen JP, Kallioinen M, Kubin ME, Greco D, Tasanen K, Alenius H, Bertino B, Carlavan I, Mehul B, Deret S, Reiniche P, Martel P, Marty C, Blume-Peytavi U, Voegel JJ, Lauerma A (2014) IL-17/Th17 pathway is activated in acne lesions. PLoS O ne 9:e105238. https://doi.org/10.1371/journal.pone.0105238

    Article  CAS  Google Scholar 

  15. Kim HJ, Song SB, Yang Y, Eun YS, Cho BK, Park HJ, Cho DH (2011) Erythroid differentiation regulator 1 (Erdr1) is a proapototic factor in human keratinocytes. Exp Dermatol 20:920–925. https://doi.org/10.1111/j.1600-0625.2011.01354.x

    Article  CAS  PubMed  Google Scholar 

  16. Kim KE, Houh Y, Lee J, Kim S, Cho D, Park HJ (2016) Downregulation of erythroid differentiation regulator 1 (Erdr1) plays a critical role in psoriasis pathogene. Exp Dermatol 25:570–572. https://doi.org/10.1111/exd.13005

    Article  PubMed  Google Scholar 

  17. Kim KE, Houh Y, Park HJ, Cho D (2016) Therapeutic effects of erythroid differentiation regulator 1 on imiquimod-induced psoriasis-like skin inflammation. Int J Mol Sci 17:244. https://doi.org/10.3390/ijms17020244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kim M, Kim KE, Jung HY, Jo H, Jeong SW, Lee J, Kim CH, Kim H, Cho D, Park HJ (2015) Erythroid differentiation regulator 1 inhibits both inflammation and angiogenesis in a mouse model of rosacea. Exp Dermatol 24:680–685. https://doi.org/10.1111/exd.12745

    Article  CAS  PubMed  Google Scholar 

  19. Kuroda K, Tajima S (2004) HSP47 is a useful marker for skin fibroblasts in formalin-fixed, paraffin-embedded tissue specimens. J Cutan Pathol 31:241–246

    Article  CAS  Google Scholar 

  20. Lakos G, Takagawa S, Chen SJ, Ferreira AM, Han G, Masuda K, Wang XJ, DiPietro LA, Varga J (2004) Targeted disruption of TGF-beta/Smad3 signaling modulates skin fibrosis in a mouse model of scleroderma. Am J Pathol 165:203–217

    Article  CAS  Google Scholar 

  21. Midwood KS, Williams LV, Schwarzbauer JE (2004) Tissue repair and the dynamics of the extracellular matrix. Int J Biochem Cell Biol 36:1031–1037. https://doi.org/10.1016/j.biocel.2003.12.003

    Article  CAS  PubMed  Google Scholar 

  22. Monaco JL, Lawrence WT (2003) Acute wound healing an overview. Clin Plast Surg 30:1–12

    Article  Google Scholar 

  23. Nakao A, Imamura T, Souchelnytskyi S, Kawabata M, Ishisaki A, Oeda E, Tamaki K, Hanai J, Heldin CH, Miyazono K, ten Dijke P (1997) TGF-beta receptor-mediated signalling Smad2, Smad3 and Smad4. EMBO J 16:5353–5362. https://doi.org/10.1093/emboj/16.17.5353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ochsendorf F (2006) Systemic antibiotic therapy of acne vulgaris. J Dtsch Dermatol Ges 4:828–841. https://doi.org/10.1111/j.1610-0387.2006.06053.x

    Article  PubMed  Google Scholar 

  25. Penn JW, Grobbelaar AO, Rolfe KJ (2012) The role of the TGF-beta family in wound healing, burns and scarring: a review. Int J Burns Trauma 2:18–28

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Pletzel D, Mansour SC, Wuerth K, Rahanjam N, Hancock RE (2017) New mouse model for chronic infections by gram-negative bacteria enabling the study of anti-infective efficacy and host-microbe interactions. MBio 8:e00140-17. https://doi.org/10.1128/mBio.00140-17

    Article  Google Scholar 

  27. Quan T, Wang F, Shao Y, Rittié L, Xia W, Orringer JS, Voorhees JJ, Fisher GJ (2013) Enhancing structural support of the dermal microenvironment activates fibroblasts, endothelial cells, and keratinocytes in aged human skin in vivo. J Investig Dermatol 133:658–667. https://doi.org/10.1038/jid.2012.364

    Article  CAS  PubMed  Google Scholar 

  28. Schiller M, Dennler S, Anderegg U, Kokot A, Simon JC, Luger TA, Mauviel A, Bohm M (2010) Increased cAMP levels modulate transforming growth factor-beta/Smad-induced expression of extracellular matrix components and other key fibroblast effector functions. J Biol Chem 285:409–421. https://doi.org/10.1074/jbc.M109.038620

    Article  CAS  PubMed  Google Scholar 

  29. Tan JK, Bhate K (2015) A global perspective on the epidemiology of acne. Br J Dermatol 172(Suppl 1):3–12. https://doi.org/10.1111/bjd.13462

    Article  PubMed  Google Scholar 

  30. Webster GF (1995) Inflammation in acne vulgaris. J Am Acad Dermatol 33:247–253. https://doi.org/10.1016/0190-9622(95)90243-0

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This research was supported by Creative Materials Discovery Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (2016M3D1A1021387) and Korea Drug Development Fund funded by Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare (KDDF-201612-09, Republic of Korea).

Author information

Author notes

  1. Eun-Yeung Gong and Sora Lee contributed equally Co-first authors:.

  2. Daeho Cho and HyunJeong Park contributed equally to this work.

Authors and Affiliations

  1. Institute of Convergence Science, Korea University, Anam-ro 145, Seongbuk-gu, Seoul, 02841, Republic of Korea

    Eun-Yeung Gong, Sunyoung Park, Myun Soo Kim & Daeho Cho

  2. Kine Sciences, 525, Seolleung-ro, Gangnam-gu, Seoul, 06149, Republic of Korea

    Sora Lee, Sunyoung Park, Myun Soo Kim & Daeho Cho

  3. Department of Cosmetic Science, Sookmyung Women’s University, Chungpa-Dong 2-Ka, Yongsan-gu, Seoul, 04310, Republic of Korea

    Kyung Eun Kim

  4. Department of Anatomy, Inje College of Medicine, 75, Bokji-ro, Busanjin-gu, Busan, 47392, Republic of Korea

    Daejin Kim

  5. Department of Dermatology, College of Medicine, Yeouido St. Mary’s Hospital, The Catholic University of Korea, 10, 63-ro, Yeongdeungpo-gu, Seoul, 07345, Republic of Korea

    Hyun Jeong Park

Authors
  1. Eun-Yeung Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sora Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sunyoung Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kyung Eun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Myun Soo Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Daejin Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hyun Jeong Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Daeho Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Hyun Jeong Park or Daeho Cho.

Ethics declarations

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

The animal study was approved by the Industry Academic Cooperation Foundation at Sookmyung Women’s University, Republic of Korea (Approval number: SMU-IACUC-1612-038).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gong, EY., Lee, S., Park, S. et al. Erythroid differentiation regulator 1 (Erdr1) enhances wound healing through collagen synthesis in acne skin. Arch Dermatol Res 312, 59–67 (2020). https://doi.org/10.1007/s00403-019-01980-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-019-01980-3

Keywords

Search

Navigation