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Tetraspanin CD9 Regulates Cell Contraction and Actin Arrangement via RhoA in Human Vascular Smooth Muscle Cells
The most prevalent cardiovascular diseases arise from alterations in vascular smooth muscle cell (VSMC) morphology and function. Tetraspanin CD9 has been previously implicated in regulating vascular pathologies; however, insight into how CD9 may regulate adverse VSMC phenotypes has not been provided...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4153684/ https://www.ncbi.nlm.nih.gov/pubmed/25184334 http://dx.doi.org/10.1371/journal.pone.0106999 |
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author | Herr, Michael J. Mabry, Scott E. Jennings, Lisa K. |
author_facet | Herr, Michael J. Mabry, Scott E. Jennings, Lisa K. |
author_sort | Herr, Michael J. |
collection | PubMed |
description | The most prevalent cardiovascular diseases arise from alterations in vascular smooth muscle cell (VSMC) morphology and function. Tetraspanin CD9 has been previously implicated in regulating vascular pathologies; however, insight into how CD9 may regulate adverse VSMC phenotypes has not been provided. We utilized a human model of aortic smooth muscle cells to understand the consequences of CD9 deficiency on VSMC phenotypes. Upon knocking down CD9, the cells developed an abnormally small and rounded morphology. We determined that this morphological change was due to a lack of typical parallel actin arrangement. We also found similar total RhoA but decreased GTP-bound (active) RhoA levels in CD9 deficient cells. As a result, cells lacking a full complement of CD9 were less contractile than their control treated counterparts. Upon restoration of RhoA activity in the CD9 deficient cells, the phenotype was reversed and cell contraction was restored. Conversely, inhibition of RhoA activity in the control cells mimicked the CD9-deficient cell phenotype. Thus, alteration in CD9 expression was sufficient to profoundly disrupt cellular actin arrangement and endogenous cell contraction by interfering with RhoA signaling. This study provides insight into how CD9 may regulate previously described vascular smooth muscle cell pathophysiology. |
format | Online Article Text |
id | pubmed-4153684 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-41536842014-09-05 Tetraspanin CD9 Regulates Cell Contraction and Actin Arrangement via RhoA in Human Vascular Smooth Muscle Cells Herr, Michael J. Mabry, Scott E. Jennings, Lisa K. PLoS One Research Article The most prevalent cardiovascular diseases arise from alterations in vascular smooth muscle cell (VSMC) morphology and function. Tetraspanin CD9 has been previously implicated in regulating vascular pathologies; however, insight into how CD9 may regulate adverse VSMC phenotypes has not been provided. We utilized a human model of aortic smooth muscle cells to understand the consequences of CD9 deficiency on VSMC phenotypes. Upon knocking down CD9, the cells developed an abnormally small and rounded morphology. We determined that this morphological change was due to a lack of typical parallel actin arrangement. We also found similar total RhoA but decreased GTP-bound (active) RhoA levels in CD9 deficient cells. As a result, cells lacking a full complement of CD9 were less contractile than their control treated counterparts. Upon restoration of RhoA activity in the CD9 deficient cells, the phenotype was reversed and cell contraction was restored. Conversely, inhibition of RhoA activity in the control cells mimicked the CD9-deficient cell phenotype. Thus, alteration in CD9 expression was sufficient to profoundly disrupt cellular actin arrangement and endogenous cell contraction by interfering with RhoA signaling. This study provides insight into how CD9 may regulate previously described vascular smooth muscle cell pathophysiology. Public Library of Science 2014-09-03 /pmc/articles/PMC4153684/ /pubmed/25184334 http://dx.doi.org/10.1371/journal.pone.0106999 Text en © 2014 Herr et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Herr, Michael J. Mabry, Scott E. Jennings, Lisa K. Tetraspanin CD9 Regulates Cell Contraction and Actin Arrangement via RhoA in Human Vascular Smooth Muscle Cells |
title | Tetraspanin CD9 Regulates Cell Contraction and Actin Arrangement via RhoA in Human Vascular Smooth Muscle Cells |
title_full | Tetraspanin CD9 Regulates Cell Contraction and Actin Arrangement via RhoA in Human Vascular Smooth Muscle Cells |
title_fullStr | Tetraspanin CD9 Regulates Cell Contraction and Actin Arrangement via RhoA in Human Vascular Smooth Muscle Cells |
title_full_unstemmed | Tetraspanin CD9 Regulates Cell Contraction and Actin Arrangement via RhoA in Human Vascular Smooth Muscle Cells |
title_short | Tetraspanin CD9 Regulates Cell Contraction and Actin Arrangement via RhoA in Human Vascular Smooth Muscle Cells |
title_sort | tetraspanin cd9 regulates cell contraction and actin arrangement via rhoa in human vascular smooth muscle cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4153684/ https://www.ncbi.nlm.nih.gov/pubmed/25184334 http://dx.doi.org/10.1371/journal.pone.0106999 |
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