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MRTF: Basic Biology and Role in Kidney Disease
A lesser known but crucially important downstream effect of Rho family GTPases is the regulation of gene expression. This major role is mediated via the cytoskeleton, the organization of which dictates the nucleocytoplasmic shuttling of a set of transcription factors. Central among these is myocardi...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199744/ https://www.ncbi.nlm.nih.gov/pubmed/34204945 http://dx.doi.org/10.3390/ijms22116040 |
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author | Miranda, Maria Zena Lichner, Zsuzsanna Szászi, Katalin Kapus, András |
author_facet | Miranda, Maria Zena Lichner, Zsuzsanna Szászi, Katalin Kapus, András |
author_sort | Miranda, Maria Zena |
collection | PubMed |
description | A lesser known but crucially important downstream effect of Rho family GTPases is the regulation of gene expression. This major role is mediated via the cytoskeleton, the organization of which dictates the nucleocytoplasmic shuttling of a set of transcription factors. Central among these is myocardin-related transcription factor (MRTF), which upon actin polymerization translocates to the nucleus and binds to its cognate partner, serum response factor (SRF). The MRTF/SRF complex then drives a large cohort of genes involved in cytoskeleton remodeling, contractility, extracellular matrix organization and many other processes. Accordingly, MRTF, activated by a variety of mechanical and chemical stimuli, affects a plethora of functions with physiological and pathological relevance. These include cell motility, development, metabolism and thus metastasis formation, inflammatory responses and—predominantly-organ fibrosis. The aim of this review is twofold: to provide an up-to-date summary about the basic biology and regulation of this versatile transcriptional coactivator; and to highlight its principal involvement in the pathobiology of kidney disease. Acting through both direct transcriptional and epigenetic mechanisms, MRTF plays a key (yet not fully appreciated) role in the induction of a profibrotic epithelial phenotype (PEP) as well as in fibroblast-myofibroblast transition, prime pathomechanisms in chronic kidney disease and renal fibrosis. |
format | Online Article Text |
id | pubmed-8199744 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81997442021-06-14 MRTF: Basic Biology and Role in Kidney Disease Miranda, Maria Zena Lichner, Zsuzsanna Szászi, Katalin Kapus, András Int J Mol Sci Review A lesser known but crucially important downstream effect of Rho family GTPases is the regulation of gene expression. This major role is mediated via the cytoskeleton, the organization of which dictates the nucleocytoplasmic shuttling of a set of transcription factors. Central among these is myocardin-related transcription factor (MRTF), which upon actin polymerization translocates to the nucleus and binds to its cognate partner, serum response factor (SRF). The MRTF/SRF complex then drives a large cohort of genes involved in cytoskeleton remodeling, contractility, extracellular matrix organization and many other processes. Accordingly, MRTF, activated by a variety of mechanical and chemical stimuli, affects a plethora of functions with physiological and pathological relevance. These include cell motility, development, metabolism and thus metastasis formation, inflammatory responses and—predominantly-organ fibrosis. The aim of this review is twofold: to provide an up-to-date summary about the basic biology and regulation of this versatile transcriptional coactivator; and to highlight its principal involvement in the pathobiology of kidney disease. Acting through both direct transcriptional and epigenetic mechanisms, MRTF plays a key (yet not fully appreciated) role in the induction of a profibrotic epithelial phenotype (PEP) as well as in fibroblast-myofibroblast transition, prime pathomechanisms in chronic kidney disease and renal fibrosis. MDPI 2021-06-03 /pmc/articles/PMC8199744/ /pubmed/34204945 http://dx.doi.org/10.3390/ijms22116040 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Miranda, Maria Zena Lichner, Zsuzsanna Szászi, Katalin Kapus, András MRTF: Basic Biology and Role in Kidney Disease |
title | MRTF: Basic Biology and Role in Kidney Disease |
title_full | MRTF: Basic Biology and Role in Kidney Disease |
title_fullStr | MRTF: Basic Biology and Role in Kidney Disease |
title_full_unstemmed | MRTF: Basic Biology and Role in Kidney Disease |
title_short | MRTF: Basic Biology and Role in Kidney Disease |
title_sort | mrtf: basic biology and role in kidney disease |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199744/ https://www.ncbi.nlm.nih.gov/pubmed/34204945 http://dx.doi.org/10.3390/ijms22116040 |
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