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Pigment epithelium derived factor as a novel multi-target treatment for uterine fibroids.
Reprod Biomed Online. 2020 Aug; 41(2):335-342.RB

Abstract

RESEARCH QUESTION

Does recombinant pigment epithelium derived factor (PEDF) have potential in treating uterine fibroids?

DESIGN

In-vitro models that used human leiomyoma and Eker rat uterine leiomyoma (ELT-3) cell lines. The ELT-3 cell line was used to examine cellular targets after adding recombinant PEDF to the culture media. Athymic nude female mice were used as an in-vivo model. They were injected with ELT-3 cells to induce ectopic fibroid lesions, then treated with recombinant PEDF.

RESULTS

RNA expression of PEDF and its receptors was found in both leiomyoma cell lines, as well as the expression of PEDF receptors. Addition of recombinant PEDF to the culture medium of leiomyoma cell lines activated ERK in a time-dependent manner, induced down-regulation of vascular endothelial growth factor mRNA and protein, as well as the mRNAs of oestrogen receptors alpha and beta and inhibited cellular proliferation. Treatment of mice-bearing fibroids with recombinant PEDF reduced fibroid growth rate and resulted in smaller tumours.

CONCLUSIONS

This study suggests that recombinant PEDF is a putative novel potent physiological treatment for uterine fibroids. It targets several cornerstones of fibroid pathobiology in parallel, including vascular endothelial growth factor and oestrogen receptors, which are needed for vascularization, and restricts fibroid growth and final size in an animal model.

Authors+Show Affiliations

Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Ramat-Aviv, Israel.Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Ramat-Aviv, Israel.Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Ramat-Aviv, Israel.IVF and Infertility Unit, Department of Obstetrics and Gynecology, Shaare Zedek Medical Center, affiliated with the Hebrew University Medical School of Jerusalem Jerusalem, Israel. Electronic address: idoba@szmc.org.il.Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Ramat-Aviv, Israel.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32532667

Citation

Bar-Joseph, Hadas, et al. "Pigment Epithelium Derived Factor as a Novel Multi-target Treatment for Uterine Fibroids." Reproductive Biomedicine Online, vol. 41, no. 2, 2020, pp. 335-342.
Bar-Joseph H, Hikri E, Chuderland D, et al. Pigment epithelium derived factor as a novel multi-target treatment for uterine fibroids. Reprod Biomed Online. 2020;41(2):335-342.
Bar-Joseph, H., Hikri, E., Chuderland, D., Ben-Ami, I., & Shalgi, R. (2020). Pigment epithelium derived factor as a novel multi-target treatment for uterine fibroids. Reproductive Biomedicine Online, 41(2), 335-342. https://doi.org/10.1016/j.rbmo.2020.03.024
Bar-Joseph H, et al. Pigment Epithelium Derived Factor as a Novel Multi-target Treatment for Uterine Fibroids. Reprod Biomed Online. 2020;41(2):335-342. PubMed PMID: 32532667.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pigment epithelium derived factor as a novel multi-target treatment for uterine fibroids. AU - Bar-Joseph,Hadas, AU - Hikri,Elad, AU - Chuderland,Dana, AU - Ben-Ami,Ido, AU - Shalgi,Ruth, Y1 - 2020/04/29/ PY - 2019/12/05/received PY - 2020/03/12/revised PY - 2020/03/31/accepted PY - 2020/6/14/pubmed PY - 2020/6/14/medline PY - 2020/6/14/entrez KW - Angiogenesis KW - Estrogen receptor KW - PEDF KW - Proliferation KW - Uterine fibroids, VEGF SP - 335 EP - 342 JF - Reproductive biomedicine online JO - Reprod. Biomed. Online VL - 41 IS - 2 N2 - RESEARCH QUESTION: Does recombinant pigment epithelium derived factor (PEDF) have potential in treating uterine fibroids? DESIGN: In-vitro models that used human leiomyoma and Eker rat uterine leiomyoma (ELT-3) cell lines. The ELT-3 cell line was used to examine cellular targets after adding recombinant PEDF to the culture media. Athymic nude female mice were used as an in-vivo model. They were injected with ELT-3 cells to induce ectopic fibroid lesions, then treated with recombinant PEDF. RESULTS: RNA expression of PEDF and its receptors was found in both leiomyoma cell lines, as well as the expression of PEDF receptors. Addition of recombinant PEDF to the culture medium of leiomyoma cell lines activated ERK in a time-dependent manner, induced down-regulation of vascular endothelial growth factor mRNA and protein, as well as the mRNAs of oestrogen receptors alpha and beta and inhibited cellular proliferation. Treatment of mice-bearing fibroids with recombinant PEDF reduced fibroid growth rate and resulted in smaller tumours. CONCLUSIONS: This study suggests that recombinant PEDF is a putative novel potent physiological treatment for uterine fibroids. It targets several cornerstones of fibroid pathobiology in parallel, including vascular endothelial growth factor and oestrogen receptors, which are needed for vascularization, and restricts fibroid growth and final size in an animal model. SN - 1472-6491 UR - https://www.unboundmedicine.com/medline/citation/32532667/Pigment_epithelium_derived_factor_as_a_novel_multi-target_treatment_for_uterine_fibroids L2 - https://linkinghub.elsevier.com/retrieve/pii/S1472-6483(20)30179-6 DB - PRIME DP - Unbound Medicine ER -
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