Targeting anthrax toxin receptor 2 ameliorates endometriosis progression

Shih-Chieh Lin, Hsiu Chi Lee, Ching Ting Hsu, Yi Han Huang, Wan Ning Li, Pei Ling Hsu, Meng-Hsing Wu, Shaw-Jenq Tsai

Research output: Contribution to journalArticle

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Abstract

Rationale: Endometriosis is a highly prevalent gynecological disease in women of reproductive age that markedly reduces life quality and fertility. Unfortunately, there is no cure for this disease, which highlights that more efforts are needed to investigate the underlying mechanism for designing novel therapeutic regimens. This study aims to investigate druggable membrane receptors distinctively expressed in endometriotic cells. Methods: Bioinformatic analysis of public databases was employed to identify potential druggable candidates. Normal endometrial tissues and ectopic endometriotic lesions were obtained for the determination of target genes. Primary endometrial and endometriotic stromal cells as well as two different mouse models of endometriosis were used to characterize molecular mechanisms and therapeutic outcomes of endometriosis, respectively. Results: Anthrax toxin receptor 2 (ANTXR2) mRNA and protein are upregulated in the endometriotic specimens. Elevation of ANTXR2 promotes endometriotic cell adhesion, proliferation, and angiogenesis. Furthermore, hypoxia is the driving force for ANTXR2 upregulation via altering histone modification of ANTXR2 promoter by reducing the repressive mark, histone H3 lysine 27 (H3K27) trimethylation, and increasing the active mark, H3K4 trimethylation. Activation of ANTXR2 signaling leads to increased Yes-associated protein 1 (YAP1) nuclear translocation and transcriptional activity, which contributes to numerous pathological processes of endometriosis. Pharmacological blocking of ANTXR2 signaling not only prevents endometriotic lesion development but also causes the regression of established lesion. Conclusion: Taken together, we have identified a novel target that contributes to the disease pathogenesis of endometriosis and provided a potential therapeutic regimen to treat it.

Original languageEnglish
Pages (from-to)620-632
Number of pages13
JournalTheranostics
Volume9
Issue number3
DOIs
Publication statusPublished - 2019 Jan 1

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Endometriosis
Histone Code
Choristoma
Pathologic Processes
Stromal Cells
Nuclear Proteins
Computational Biology
Cell Adhesion
Histones
Lysine
Fertility
anthrax toxin receptors
Up-Regulation
Therapeutics
Quality of Life
Cell Proliferation
Databases
Pharmacology
Messenger RNA
Membranes

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

Cite this

Lin, Shih-Chieh ; Lee, Hsiu Chi ; Hsu, Ching Ting ; Huang, Yi Han ; Li, Wan Ning ; Hsu, Pei Ling ; Wu, Meng-Hsing ; Tsai, Shaw-Jenq. / Targeting anthrax toxin receptor 2 ameliorates endometriosis progression. In: Theranostics. 2019 ; Vol. 9, No. 3. pp. 620-632.
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Targeting anthrax toxin receptor 2 ameliorates endometriosis progression. / Lin, Shih-Chieh; Lee, Hsiu Chi; Hsu, Ching Ting; Huang, Yi Han; Li, Wan Ning; Hsu, Pei Ling; Wu, Meng-Hsing; Tsai, Shaw-Jenq.

In: Theranostics, Vol. 9, No. 3, 01.01.2019, p. 620-632.

Research output: Contribution to journalArticle

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