Skip to main content

Advertisement

Log in

The Effects of Periostin Expression on Fibroid-Like Transition of Myometrial Cells

  • Fibroids: Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Fibroids, benign tumors of the myometrium, are the most common tumors in women and are associated with spontaneous abortion, preterm birth, placenta abruption, and infertility, among others. The incidence of fibroids in reproductive aged women is 20–89%. Fibroids are characterized by high production of extracellular matrix (ECM), particularly collagens, which play a role in their growth. However, their pathogenesis is poorly understood. Recently, we and others have found periostin (POSTN), a regulatory ECM protein, to be overexpressed in the majority of fibroids analyzed. Periostin is an ECM protein that is a critical regulator and well-established biomarker for fibrosis in tissues such as the lung, skin, and kidney. Our hypothesis was that periostin plays a role in the fibrotic transition of myometrial cells to fibroid cells. To test this, we evaluated the effects of POSTN overexpression in myometrial cells. Telomerase-immortalized myometrial cells were transduced with control or POSTN-overexpression lentivirus particles, generating one control (dCas9-Mock) and two overexpression (dCas9-POSTN-01, dCas9-POSTN-02) cell lines. Overexpression of POSTN in immortalized myometrial cells resulted in a change in phenotype consistent with fibroid cells. They upregulated expression of key fibroid genes and had increased proliferation, adhesion, and migration in vitro. Here, we show a potential role for periostin in the transition of myometrial cells to fibroid cells, giving rationale for future investigation into the role of periostin in fibroid pathogenesis and its potential as a therapeutic target.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data Availability

The dataset analyzed in this study was first published in [1] and is available at NCBI without restriction at https://www.ncbi.nlm.nih.gov/sra/?term=SRP166862 and https://www.ncbi.nlm.nih.gov/sra/?term=SRP217468

Code Availability

This is not applicable.

References

  1. George JW, Fan H, Johnson B, Carpenter TJ, Foy KK, Chatterjee A, Patterson AL, Koeman J, Adams M, Madaj ZB, Chesla D, Marsh EE, Triche TJ, Shen H, Teixeira JM. Integrated epigenome, exome, and transcriptome analyses reveal molecular subtypes and homeotic transformation in uterine fibroids. Cell Rep. 2019;29(4069–4085): e6.

    Google Scholar 

  2. Baird DD, Dunson DB, Hill MC, Cousins D, Schectman JM. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol. 2003;188:100–7.

    Article  PubMed  Google Scholar 

  3. Borgfeldt C, Andolf E. Transvaginal ultrasonographic findings in the uterus and the endometrium: low prevalence of leiomyoma in a random sample of women age 25–40 years. Acta Obstet Gynecol Scand. 2000;79:202–7.

    CAS  PubMed  Google Scholar 

  4. Cramer SF, Patel A. The frequency of uterine leiomyomas. Am J Clin Pathol. 1990;94:435–8.

    Article  CAS  PubMed  Google Scholar 

  5. Commandeur AE, Styer AK, Teixeira JM. Epidemiological and genetic clues for molecular mechanisms involved in uterine leiomyoma development and growth. Hum Reprod Update. 2015;21:593–615.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Wise LA, Laughlin-Tommaso SK. Epidemiology of uterine fibroids: from menarche to menopause. Clin Obstet Gynecol. 2016;59:2–24.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Chabbert-Buffet N, Esber N, Bouchard P. Fibroid growth and medical options for treatment. Fertil Steril. 2014;102:630–9.

    Article  PubMed  Google Scholar 

  8. Gorny KR, Borah BJ, Brown DL, Woodrum DA, Stewart EA, Hesley GK. Incidence of additional treatments in women treated with MR-guided focused US for symptomatic uterine fibroids: review of 138 patients with an average follow-up of 2.8 years. J Vasc Interv Radiol. 2014;25:1506–1512.

  9. Makinen N, Mehine M, Tolvanen J, Kaasinen E, Li Y, Lehtonen HJ, Gentile M, Yan J, Enge M, Taipale M, Aavikko M, Katainen R, Virolainen E, Bohling T, Koski TA, Launonen V, Sjoberg J, Taipale J, Vahteristo P, Aaltonen LA. MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas. Science. 2011;334:252–5.

    Article  PubMed  Google Scholar 

  10. Heinonen HR, Sarvilinna NS, Sjoberg J, Kampjarvi K, Pitkanen E, Vahteristo P, Makinen N, Aaltonen LA. MED12 mutation frequency in unselected sporadic uterine leiomyomas. Fertil Steril. 2014;102:1137–42.

    Article  CAS  PubMed  Google Scholar 

  11. Markowski DN, Helmke BM, Bartnitzke S, Loning T, Bullerdiek J. Uterine fibroids: do we deal with more than one disease? Int J Gynecol Pathol. 2014;33:568–72.

    Article  CAS  PubMed  Google Scholar 

  12. Mehine M, Makinen N, Heinonen HR, Aaltonen LA, Vahteristo P. Genomics of uterine leiomyomas: insights from high-throughput sequencing. Fertil Steril. 2014;102:621–9.

    Article  CAS  PubMed  Google Scholar 

  13. Jamaluddin MFB, Ko YA, Kumar M, Brown Y, Bajwa P, Nagendra PB, Skerrett-Byrne DA, Hondermarck H, Baker MA, Dun MD, Scott RJ, Nahar P, Tanwar PS. Proteomic profiling of human uterine fibroids reveals upregulation of the extracellular matrix protein periostin. Endocrinology. 2018;159:1106–18.

    Article  CAS  PubMed  Google Scholar 

  14. Roberts DD. Emerging functions of matricellular proteins. Cell Mol Life Sci. 2011;68:3133.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ciarmela P, Islam MS, Reis FM, Gray PC, Bloise E, Petraglia F, Vale W, Castellucci M. Growth factors and myometrium: biological effects in uterine fibroid and possible clinical implications. Hum Reprod Update. 2011;17:772–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Murota H, Lingli Y, Katayama I. Periostin in the pathogenesis of skin diseases. Cell Mol Life Sci. 2017;74:4321–8.

    Article  CAS  PubMed  Google Scholar 

  17. Zhang Z, Nie F, Kang C, Chen B, Qin Z, Ma J, Ma Y, Zhao X. Increased periostin expression affects the proliferation, collagen synthesis, migration and invasion of keloid fibroblasts under hypoxic conditions. Int J Mol Med. 2014;34:253–61.

    Article  PubMed  Google Scholar 

  18. Yang L, Serada S, Fujimoto M, Terao M, Kotobuki Y, Kitaba S, Matsui S, Kudo A, Naka T, Murota H, Katayama I. Periostin facilitates skin sclerosis via PI3K/Akt dependent mechanism in a mouse model of scleroderma. PLoS ONE. 2012;7:e41994.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Zhou HM, Wang J, Elliott C, Wen W, Hamilton DW, Conway SJ. Spatiotemporal expression of periostin during skin development and incisional wound healing: lessons for human fibrotic scar formation. J Cell Commun Signal. 2010;4:99–107.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Carney SA, Tahara H, Swartz CD, Risinger JI, He H, Moore AB, Haseman JK, Barrett JC, Dixon D. Immortalization of human uterine leiomyoma and myometrial cell lines after induction of telomerase activity: molecular and phenotypic characteristics. Lab Invest. 2002;82:719–28.

    Article  CAS  PubMed  Google Scholar 

  21. Grada A, Otero-Vinas M, Prieto-Castrillo F, Obagi Z, Falanga V. Research techniques made simple: analysis of collective cell migration using the wound healing assay. J Invest Dermatol. 2017;137:e11–6.

    Article  CAS  PubMed  Google Scholar 

  22. Raspotnig G, Fauler G, Jantscher A, Windischhofer W, Schachl K, Leis HJ. Colorimetric determination of cell numbers by Janus green staining. Anal Biochem. 1999;275:74–83.

    Article  CAS  PubMed  Google Scholar 

  23. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65:55–63.

    Article  CAS  PubMed  Google Scholar 

  24. Conway SJ, Izuhara K, Kudo Y, Litvin J, Markwald R, Ouyang G, Arron JR, Holweg CTJ, Kudo A. The role of periostin in tissue remodeling across health and disease. Cell Mol Life Sci. 2014;71:1279–88.

    Article  CAS  PubMed  Google Scholar 

  25. Kavvadas P, Dussaule JC, Chatziantoniou C. Searching novel diagnostic markers and targets for therapy of CKD. Kidney Int Suppl. 2011;2014(4):53–7.

    Google Scholar 

  26. Sidhu SS, Yuan S, Innes AL, Kerr S, Woodruff PG, Hou L, Muller SJ, Fahy JV. Roles of epithelial cell-derived periostin in TGF-beta activation, collagen production, and collagen gel elasticity in asthma. Proc Natl Acad Sci U S A. 2010;107:14170–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kim JJ, Kurita T, Bulun SE. Progesterone action in endometrial cancer, endometriosis, uterine fibroids, and breast cancer. Endocr Rev. 2013;34:130–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Bulun SE, Moravek MB, Yin P, Ono M, Coon JS, Dyson MT, Navarro A, Marsh EE, Zhao H, Maruyama T, Chakravarti D, Kim JJ, Wei JJ. Uterine leiomyoma stem cells: linking progesterone to growth. Semin Reprod Med. 2015;33:357–65.

  29. Zheng LH, Cai FF, Ge I, Biskup E, Cheng ZP. Stromal fibroblast activation and their potential association with uterine fibroids (Review). Oncol Lett. 2014;8:479–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Carrino DA, Mesiano S, Barker NM, Hurd WW, Caplan AI. Proteoglycans of uterine fibroids and keloid scars: similarity in their proteoglycan composition. Biochem J. 2012;443:361–8.

    Article  CAS  PubMed  Google Scholar 

  31. Yin SL, Qin ZL, Yang X. Role of periostin in skin wound healing and pathologic scar formation. Chin Med J (Engl). 2020;133:2236–8.

    Article  CAS  PubMed  Google Scholar 

  32. Hinz B. The role of myofibroblasts in wound healing. Curr Res Transl Med. 2016;64:171–7.

    Article  CAS  PubMed  Google Scholar 

  33. Hamilton DW. Functional role of periostin in development and wound repair: implications for connective tissue disease. J Cell Commun Signal. 2008;2:9–17.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Liu AY, Zheng H, Ouyang G. Periostin, a multifunctional matricellular protein in inflammatory and tumor microenvironments. Matrix Biol. 2014;37:150–6.

    Article  PubMed  Google Scholar 

  35. Zhu M, Saxton RE, Ramos L, Chang DD, Karlan BY, Gasson JC, Slamon DJ. Neutralizing monoclonal antibody to periostin inhibits ovarian tumor growth and metastasis. Mol Cancer Ther. 2011;10:1500–8.

    Article  CAS  PubMed  Google Scholar 

  36. Tai IT, Dai M, Chen LB. Periostin induction in tumor cell line explants and inhibition of in vitro cell growth by anti-periostin antibodies. Carcinogenesis. 2005;26:908–15.

    Article  CAS  PubMed  Google Scholar 

  37. Yokota K, Kobayakawa K, Saito T, Hara M, Kijima K, Ohkawa Y, Harada A, Okazaki K, Ishihara K, Yoshida S, Kudo A, Iwamoto Y, Okada S. Periostin promotes scar formation through the interaction between pericytes and infiltrating monocytes/macrophages after spinal cord injury. Am J Pathol. 2017;187:639–53.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

Funding was provided by SRI and Bayer Discovery/Innovation Grant (ALP).

Author information

Authors and Affiliations

Authors

Contributions

Conceptualization was done by YYL, JG, AB, JT, and ALP. Methodology and analysis were done by YYL, JG, SL, and FW. Writing, reviewing, and editing were done by all authors.

Corresponding author

Correspondence to Amanda L. Patterson.

Ethics declarations

Ethical Approval

All protocols involving human subjects were approved by the Institutional Review Boards at the University of Missouri.

Consent to Participate

Informed consent was obtained from all individual participants included in the study.

Consent for Publication

This is not applicable.

Conflict of Interest

The authors have no relevant financial or non-financial interests to disclose.

Additional information

Publisher's Note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lenis, Y.Y., George, J.W., Lind, S. et al. The Effects of Periostin Expression on Fibroid-Like Transition of Myometrial Cells. Reprod. Sci. 30, 1616–1624 (2023). https://doi.org/10.1007/s43032-022-01128-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43032-022-01128-1

Keywords

Navigation