Benzyl butyl phthalate decreases myogenic differentiation of endometrial mesenchymal stem/stromal cells through miR-137-mediated regulation of PITX2

Abstract Phthalate, an environmental toxin, has been considered as an endocrine-disrupting chemical. Growing evidence has demonstrated links between endocrine-disrupting chemicals, tissue development, and reproductive physiology, but the mechanisms of gene expression regulation by environmental fact...

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Autores principales: Hung-Sheng Chen, Chia-Yi Hsu, Yu-Chia Chang, Hui-Yu Chuang, Cheng-Yu Long, Tsung-Hua Hsieh, Eing-Mei Tsai
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/4f3a13b219394e30ae91b95083709ba7
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spelling oai:doaj.org-article:4f3a13b219394e30ae91b95083709ba72021-12-02T11:41:10ZBenzyl butyl phthalate decreases myogenic differentiation of endometrial mesenchymal stem/stromal cells through miR-137-mediated regulation of PITX210.1038/s41598-017-00286-62045-2322https://doaj.org/article/4f3a13b219394e30ae91b95083709ba72017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00286-6https://doaj.org/toc/2045-2322Abstract Phthalate, an environmental toxin, has been considered as an endocrine-disrupting chemical. Growing evidence has demonstrated links between endocrine-disrupting chemicals, tissue development, and reproductive physiology, but the mechanisms of gene expression regulation by environmental factors that affect cell differentiation are unclear. Herein, we investigated the effects of butyl benzyl phthalate (BBP) on human endometrial mesenchymal stem/stromal cell (EN-MSC) differentiation and identified a novel signaling pathway. Differentiation of endometrial mesenchymal stem/stromal cells decreased after administration of BBP. We analyzed BBP regulation of gene expression in EN-MSC using cDNA microarrays and Ingenuity Pathway Analysis software to identify affected target genes and their biological functions. PITX2 emerged as a common gene hit from separate screens targeting skeletal and muscular disorders, cell morphology, and tissue development. BBP decreased transcription of PITX2 and elevated expression of the microRNA miR-137, the predicted upstream negative regulator of PITX2. These data indicated that BBP affects PITX2 expression through miR-137 targeting of the 3′ untranslated region of PITX2 mRNA. PITX2 down-regulation also decreased MyoD transcript levels in EN-MSC. Our results demonstrate that BBP decreases EN-MSC myogenic differentiation through up-regulation of miR-137, contribute to our understanding of EN-MSC differentiation, and underline the hazardous potential of environmental hormones.Hung-Sheng ChenChia-Yi HsuYu-Chia ChangHui-Yu ChuangCheng-Yu LongTsung-Hua HsiehEing-Mei TsaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Hung-Sheng Chen
Chia-Yi Hsu
Yu-Chia Chang
Hui-Yu Chuang
Cheng-Yu Long
Tsung-Hua Hsieh
Eing-Mei Tsai
Benzyl butyl phthalate decreases myogenic differentiation of endometrial mesenchymal stem/stromal cells through miR-137-mediated regulation of PITX2
description Abstract Phthalate, an environmental toxin, has been considered as an endocrine-disrupting chemical. Growing evidence has demonstrated links between endocrine-disrupting chemicals, tissue development, and reproductive physiology, but the mechanisms of gene expression regulation by environmental factors that affect cell differentiation are unclear. Herein, we investigated the effects of butyl benzyl phthalate (BBP) on human endometrial mesenchymal stem/stromal cell (EN-MSC) differentiation and identified a novel signaling pathway. Differentiation of endometrial mesenchymal stem/stromal cells decreased after administration of BBP. We analyzed BBP regulation of gene expression in EN-MSC using cDNA microarrays and Ingenuity Pathway Analysis software to identify affected target genes and their biological functions. PITX2 emerged as a common gene hit from separate screens targeting skeletal and muscular disorders, cell morphology, and tissue development. BBP decreased transcription of PITX2 and elevated expression of the microRNA miR-137, the predicted upstream negative regulator of PITX2. These data indicated that BBP affects PITX2 expression through miR-137 targeting of the 3′ untranslated region of PITX2 mRNA. PITX2 down-regulation also decreased MyoD transcript levels in EN-MSC. Our results demonstrate that BBP decreases EN-MSC myogenic differentiation through up-regulation of miR-137, contribute to our understanding of EN-MSC differentiation, and underline the hazardous potential of environmental hormones.
format article
author Hung-Sheng Chen
Chia-Yi Hsu
Yu-Chia Chang
Hui-Yu Chuang
Cheng-Yu Long
Tsung-Hua Hsieh
Eing-Mei Tsai
author_facet Hung-Sheng Chen
Chia-Yi Hsu
Yu-Chia Chang
Hui-Yu Chuang
Cheng-Yu Long
Tsung-Hua Hsieh
Eing-Mei Tsai
author_sort Hung-Sheng Chen
title Benzyl butyl phthalate decreases myogenic differentiation of endometrial mesenchymal stem/stromal cells through miR-137-mediated regulation of PITX2
title_short Benzyl butyl phthalate decreases myogenic differentiation of endometrial mesenchymal stem/stromal cells through miR-137-mediated regulation of PITX2
title_full Benzyl butyl phthalate decreases myogenic differentiation of endometrial mesenchymal stem/stromal cells through miR-137-mediated regulation of PITX2
title_fullStr Benzyl butyl phthalate decreases myogenic differentiation of endometrial mesenchymal stem/stromal cells through miR-137-mediated regulation of PITX2
title_full_unstemmed Benzyl butyl phthalate decreases myogenic differentiation of endometrial mesenchymal stem/stromal cells through miR-137-mediated regulation of PITX2
title_sort benzyl butyl phthalate decreases myogenic differentiation of endometrial mesenchymal stem/stromal cells through mir-137-mediated regulation of pitx2
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/4f3a13b219394e30ae91b95083709ba7
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