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Gtf2ird1-Dependent Mohawk Expression Regulates Mechanosensing Properties of the Tendon
Mechanoforces experienced by an organ are translated into biological information for cellular sensing and response. In mammals, the tendon connective tissue experiences and resists physical forces, with tendon-specific mesenchymal cells called tenocytes orchestrating extracellular matrix (ECM) turno...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4836271/ https://www.ncbi.nlm.nih.gov/pubmed/26884464 http://dx.doi.org/10.1128/MCB.00950-15 |
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author | Kayama, Tomohiro Mori, Masaki Ito, Yoshiaki Matsushima, Takahide Nakamichi, Ryo Suzuki, Hidetsugu Ichinose, Shizuko Saito, Mitsuru Marumo, Keishi Asahara, Hiroshi |
author_facet | Kayama, Tomohiro Mori, Masaki Ito, Yoshiaki Matsushima, Takahide Nakamichi, Ryo Suzuki, Hidetsugu Ichinose, Shizuko Saito, Mitsuru Marumo, Keishi Asahara, Hiroshi |
author_sort | Kayama, Tomohiro |
collection | PubMed |
description | Mechanoforces experienced by an organ are translated into biological information for cellular sensing and response. In mammals, the tendon connective tissue experiences and resists physical forces, with tendon-specific mesenchymal cells called tenocytes orchestrating extracellular matrix (ECM) turnover. We show that Mohawk (Mkx), a tendon-specific transcription factor, is essential in mechanoresponsive tenogenesis through regulation of its downstream ECM genes such as type I collagens and proteoglycans such as fibromodulin both in vivo and in vitro. Wild-type (WT) mice demonstrated an increase in collagen fiber diameter and density in response to physical treadmill exercise, whereas in Mkx(−/−) mice, tendons failed to respond to the same mechanical stimulation. Furthermore, functional screening of the Mkx promoter region identified several upstream transcription factors that regulate Mkx. In particular, general transcription factor II-I repeat domain-containing protein 1 (Gtf2ird1) that is expressed in the cytoplasm of unstressed tenocytes translocated into the nucleus upon mechanical stretching to activate the Mkx promoter through chromatin regulation. Here, we demonstrate that Gtf2ird1 is essential for Mkx transcription, while also linking mechanical forces to Mkx-mediated tendon homeostasis and regeneration. |
format | Online Article Text |
id | pubmed-4836271 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-48362712016-04-28 Gtf2ird1-Dependent Mohawk Expression Regulates Mechanosensing Properties of the Tendon Kayama, Tomohiro Mori, Masaki Ito, Yoshiaki Matsushima, Takahide Nakamichi, Ryo Suzuki, Hidetsugu Ichinose, Shizuko Saito, Mitsuru Marumo, Keishi Asahara, Hiroshi Mol Cell Biol Articles Mechanoforces experienced by an organ are translated into biological information for cellular sensing and response. In mammals, the tendon connective tissue experiences and resists physical forces, with tendon-specific mesenchymal cells called tenocytes orchestrating extracellular matrix (ECM) turnover. We show that Mohawk (Mkx), a tendon-specific transcription factor, is essential in mechanoresponsive tenogenesis through regulation of its downstream ECM genes such as type I collagens and proteoglycans such as fibromodulin both in vivo and in vitro. Wild-type (WT) mice demonstrated an increase in collagen fiber diameter and density in response to physical treadmill exercise, whereas in Mkx(−/−) mice, tendons failed to respond to the same mechanical stimulation. Furthermore, functional screening of the Mkx promoter region identified several upstream transcription factors that regulate Mkx. In particular, general transcription factor II-I repeat domain-containing protein 1 (Gtf2ird1) that is expressed in the cytoplasm of unstressed tenocytes translocated into the nucleus upon mechanical stretching to activate the Mkx promoter through chromatin regulation. Here, we demonstrate that Gtf2ird1 is essential for Mkx transcription, while also linking mechanical forces to Mkx-mediated tendon homeostasis and regeneration. American Society for Microbiology 2016-04-01 /pmc/articles/PMC4836271/ /pubmed/26884464 http://dx.doi.org/10.1128/MCB.00950-15 Text en Copyright © 2016 Kayama et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Articles Kayama, Tomohiro Mori, Masaki Ito, Yoshiaki Matsushima, Takahide Nakamichi, Ryo Suzuki, Hidetsugu Ichinose, Shizuko Saito, Mitsuru Marumo, Keishi Asahara, Hiroshi Gtf2ird1-Dependent Mohawk Expression Regulates Mechanosensing Properties of the Tendon |
title | Gtf2ird1-Dependent Mohawk Expression Regulates Mechanosensing Properties of the Tendon |
title_full | Gtf2ird1-Dependent Mohawk Expression Regulates Mechanosensing Properties of the Tendon |
title_fullStr | Gtf2ird1-Dependent Mohawk Expression Regulates Mechanosensing Properties of the Tendon |
title_full_unstemmed | Gtf2ird1-Dependent Mohawk Expression Regulates Mechanosensing Properties of the Tendon |
title_short | Gtf2ird1-Dependent Mohawk Expression Regulates Mechanosensing Properties of the Tendon |
title_sort | gtf2ird1-dependent mohawk expression regulates mechanosensing properties of the tendon |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4836271/ https://www.ncbi.nlm.nih.gov/pubmed/26884464 http://dx.doi.org/10.1128/MCB.00950-15 |
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