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.
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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
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Funding was provided by SRI and Bayer Discovery/Innovation Grant (ALP).
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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.
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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
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DOI: https://doi.org/10.1007/s43032-022-01128-1