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Microarray profiling reveals the integrated stress response is activated by halofuginone in mammary epithelial cells
BACKGROUND: The small molecule Halofuginone (HF) is a potent regulator of extracellular matrix (ECM ) gene expression and is unique in its therapeutic potential. While the basis for HF effects is unknown, inhibition of TGFβ signaling and activation of the amino acid restriction response (AAR) have b...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197508/ https://www.ncbi.nlm.nih.gov/pubmed/21974968 http://dx.doi.org/10.1186/1756-0500-4-381 |
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author | Kamberov, Yana G Kim, Jihoon Mazitschek, Ralph Kuo, Winston P Whitman, Malcolm |
author_facet | Kamberov, Yana G Kim, Jihoon Mazitschek, Ralph Kuo, Winston P Whitman, Malcolm |
author_sort | Kamberov, Yana G |
collection | PubMed |
description | BACKGROUND: The small molecule Halofuginone (HF) is a potent regulator of extracellular matrix (ECM ) gene expression and is unique in its therapeutic potential. While the basis for HF effects is unknown, inhibition of TGFβ signaling and activation of the amino acid restriction response (AAR) have been linked to HF transcriptional control of a number of ECM components and amelioration of fibrosis and alleviation of autoimmune disease by regulation of Th17 cell differentiation, respectively. The aim of this study was to generate a global expression profile of HF targets in epithelial cells to identify potential mediators of HF function in this cell type. RESULTS: We report that HF modulation of the expression of the ECM remodeling protein Mmp13 in epithelial cells is separable from previously reported effects of HF on TGFβ signal inhibition, and use microarray expression analysis to correlate this with transcriptional responses characteristic of the Integrated Stress Response (ISR). CONCLUSIONS: Our findings suggest activation of the ISR may be a common mechanism underlying HF biological effects. |
format | Online Article Text |
id | pubmed-3197508 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-31975082011-10-21 Microarray profiling reveals the integrated stress response is activated by halofuginone in mammary epithelial cells Kamberov, Yana G Kim, Jihoon Mazitschek, Ralph Kuo, Winston P Whitman, Malcolm BMC Res Notes Research Article BACKGROUND: The small molecule Halofuginone (HF) is a potent regulator of extracellular matrix (ECM ) gene expression and is unique in its therapeutic potential. While the basis for HF effects is unknown, inhibition of TGFβ signaling and activation of the amino acid restriction response (AAR) have been linked to HF transcriptional control of a number of ECM components and amelioration of fibrosis and alleviation of autoimmune disease by regulation of Th17 cell differentiation, respectively. The aim of this study was to generate a global expression profile of HF targets in epithelial cells to identify potential mediators of HF function in this cell type. RESULTS: We report that HF modulation of the expression of the ECM remodeling protein Mmp13 in epithelial cells is separable from previously reported effects of HF on TGFβ signal inhibition, and use microarray expression analysis to correlate this with transcriptional responses characteristic of the Integrated Stress Response (ISR). CONCLUSIONS: Our findings suggest activation of the ISR may be a common mechanism underlying HF biological effects. BioMed Central 2011-10-05 /pmc/articles/PMC3197508/ /pubmed/21974968 http://dx.doi.org/10.1186/1756-0500-4-381 Text en Copyright ©2011 Kamberov et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Kamberov, Yana G Kim, Jihoon Mazitschek, Ralph Kuo, Winston P Whitman, Malcolm Microarray profiling reveals the integrated stress response is activated by halofuginone in mammary epithelial cells |
title | Microarray profiling reveals the integrated stress response is activated by halofuginone in mammary epithelial cells |
title_full | Microarray profiling reveals the integrated stress response is activated by halofuginone in mammary epithelial cells |
title_fullStr | Microarray profiling reveals the integrated stress response is activated by halofuginone in mammary epithelial cells |
title_full_unstemmed | Microarray profiling reveals the integrated stress response is activated by halofuginone in mammary epithelial cells |
title_short | Microarray profiling reveals the integrated stress response is activated by halofuginone in mammary epithelial cells |
title_sort | microarray profiling reveals the integrated stress response is activated by halofuginone in mammary epithelial cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197508/ https://www.ncbi.nlm.nih.gov/pubmed/21974968 http://dx.doi.org/10.1186/1756-0500-4-381 |
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