The LIM-only protein FHL2 reduces vascular lesion formation involving inhibition of proliferation and migration of smooth muscle cells.

The LIM-only protein FHL2, also known as DRAL or SLIM3, has a function in fine-tuning multiple physiological processes. FHL2 is expressed in the vessel wall in smooth muscle cells (SMCs) and endothelial cells and conflicting data have been reported on the regulatory function of FHL2 in SMC phenotype...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Kondababu Kurakula, Mariska Vos, Iker Otermin Rubio, Goran Marinković, Reinhard Buettner, Lukas C Heukamp, Jan Stap, Vivian de Waard, Claudia M van Tiel, Carlie J M de Vries
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2014
Materias:
R
Q
Acceso en línea:https://doaj.org/article/26b213cef63945599aa7e3cec543a1a3
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:26b213cef63945599aa7e3cec543a1a3
record_format dspace
spelling oai:doaj.org-article:26b213cef63945599aa7e3cec543a1a32021-11-18T08:23:10ZThe LIM-only protein FHL2 reduces vascular lesion formation involving inhibition of proliferation and migration of smooth muscle cells.1932-620310.1371/journal.pone.0094931https://doaj.org/article/26b213cef63945599aa7e3cec543a1a32014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24736599/?tool=EBIhttps://doaj.org/toc/1932-6203The LIM-only protein FHL2, also known as DRAL or SLIM3, has a function in fine-tuning multiple physiological processes. FHL2 is expressed in the vessel wall in smooth muscle cells (SMCs) and endothelial cells and conflicting data have been reported on the regulatory function of FHL2 in SMC phenotype transition. At present the function of FHL2 in SMCs in vascular injury is unknown. Therefore, we studied the role of FHL2 in SMC-rich lesion formation. In response to carotid artery ligation FHL2-deficient (FHL2-KO) mice showed accelerated lesion formation with enhanced Ki67 expression compared with wild-type (WT)-mice. Consistent with these findings, cultured SMCs from FHL2-KO mice showed increased proliferation through enhanced phosphorylation of extracellular-regulated kinase-1/2 (ERK1/2) and induction of CyclinD1 expression. Overexpression of FHL2 in SMCs inhibited CyclinD1 expression and CyclinD1-knockdown blocked the enhanced proliferation of FHL2-KO SMCs. We also observed increased CyclinD1 promoter activity in FHL2-KO SMCs, which was reduced upon ERK1/2 inhibition. Furthermore, FHL2-KO SMCs showed enhanced migration compared with WT SMCs. In conclusion, FHL2 deficiency in mice results in exacerbated SMC-rich lesion formation involving increased proliferation and migration of SMCs via enhanced activation of the ERK1/2-CyclinD1 signaling pathway.Kondababu KurakulaMariska VosIker Otermin RubioGoran MarinkovićReinhard BuettnerLukas C HeukampJan StapVivian de WaardClaudia M van TielCarlie J M de VriesPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 4, p e94931 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Kondababu Kurakula
Mariska Vos
Iker Otermin Rubio
Goran Marinković
Reinhard Buettner
Lukas C Heukamp
Jan Stap
Vivian de Waard
Claudia M van Tiel
Carlie J M de Vries
The LIM-only protein FHL2 reduces vascular lesion formation involving inhibition of proliferation and migration of smooth muscle cells.
description The LIM-only protein FHL2, also known as DRAL or SLIM3, has a function in fine-tuning multiple physiological processes. FHL2 is expressed in the vessel wall in smooth muscle cells (SMCs) and endothelial cells and conflicting data have been reported on the regulatory function of FHL2 in SMC phenotype transition. At present the function of FHL2 in SMCs in vascular injury is unknown. Therefore, we studied the role of FHL2 in SMC-rich lesion formation. In response to carotid artery ligation FHL2-deficient (FHL2-KO) mice showed accelerated lesion formation with enhanced Ki67 expression compared with wild-type (WT)-mice. Consistent with these findings, cultured SMCs from FHL2-KO mice showed increased proliferation through enhanced phosphorylation of extracellular-regulated kinase-1/2 (ERK1/2) and induction of CyclinD1 expression. Overexpression of FHL2 in SMCs inhibited CyclinD1 expression and CyclinD1-knockdown blocked the enhanced proliferation of FHL2-KO SMCs. We also observed increased CyclinD1 promoter activity in FHL2-KO SMCs, which was reduced upon ERK1/2 inhibition. Furthermore, FHL2-KO SMCs showed enhanced migration compared with WT SMCs. In conclusion, FHL2 deficiency in mice results in exacerbated SMC-rich lesion formation involving increased proliferation and migration of SMCs via enhanced activation of the ERK1/2-CyclinD1 signaling pathway.
format article
author Kondababu Kurakula
Mariska Vos
Iker Otermin Rubio
Goran Marinković
Reinhard Buettner
Lukas C Heukamp
Jan Stap
Vivian de Waard
Claudia M van Tiel
Carlie J M de Vries
author_facet Kondababu Kurakula
Mariska Vos
Iker Otermin Rubio
Goran Marinković
Reinhard Buettner
Lukas C Heukamp
Jan Stap
Vivian de Waard
Claudia M van Tiel
Carlie J M de Vries
author_sort Kondababu Kurakula
title The LIM-only protein FHL2 reduces vascular lesion formation involving inhibition of proliferation and migration of smooth muscle cells.
title_short The LIM-only protein FHL2 reduces vascular lesion formation involving inhibition of proliferation and migration of smooth muscle cells.
title_full The LIM-only protein FHL2 reduces vascular lesion formation involving inhibition of proliferation and migration of smooth muscle cells.
title_fullStr The LIM-only protein FHL2 reduces vascular lesion formation involving inhibition of proliferation and migration of smooth muscle cells.
title_full_unstemmed The LIM-only protein FHL2 reduces vascular lesion formation involving inhibition of proliferation and migration of smooth muscle cells.
title_sort lim-only protein fhl2 reduces vascular lesion formation involving inhibition of proliferation and migration of smooth muscle cells.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doaj.org/article/26b213cef63945599aa7e3cec543a1a3
work_keys_str_mv AT kondababukurakula thelimonlyproteinfhl2reducesvascularlesionformationinvolvinginhibitionofproliferationandmigrationofsmoothmusclecells
AT mariskavos thelimonlyproteinfhl2reducesvascularlesionformationinvolvinginhibitionofproliferationandmigrationofsmoothmusclecells
AT ikeroterminrubio thelimonlyproteinfhl2reducesvascularlesionformationinvolvinginhibitionofproliferationandmigrationofsmoothmusclecells
AT goranmarinkovic thelimonlyproteinfhl2reducesvascularlesionformationinvolvinginhibitionofproliferationandmigrationofsmoothmusclecells
AT reinhardbuettner thelimonlyproteinfhl2reducesvascularlesionformationinvolvinginhibitionofproliferationandmigrationofsmoothmusclecells
AT lukascheukamp thelimonlyproteinfhl2reducesvascularlesionformationinvolvinginhibitionofproliferationandmigrationofsmoothmusclecells
AT janstap thelimonlyproteinfhl2reducesvascularlesionformationinvolvinginhibitionofproliferationandmigrationofsmoothmusclecells
AT viviandewaard thelimonlyproteinfhl2reducesvascularlesionformationinvolvinginhibitionofproliferationandmigrationofsmoothmusclecells
AT claudiamvantiel thelimonlyproteinfhl2reducesvascularlesionformationinvolvinginhibitionofproliferationandmigrationofsmoothmusclecells
AT carliejmdevries thelimonlyproteinfhl2reducesvascularlesionformationinvolvinginhibitionofproliferationandmigrationofsmoothmusclecells
AT kondababukurakula limonlyproteinfhl2reducesvascularlesionformationinvolvinginhibitionofproliferationandmigrationofsmoothmusclecells
AT mariskavos limonlyproteinfhl2reducesvascularlesionformationinvolvinginhibitionofproliferationandmigrationofsmoothmusclecells
AT ikeroterminrubio limonlyproteinfhl2reducesvascularlesionformationinvolvinginhibitionofproliferationandmigrationofsmoothmusclecells
AT goranmarinkovic limonlyproteinfhl2reducesvascularlesionformationinvolvinginhibitionofproliferationandmigrationofsmoothmusclecells
AT reinhardbuettner limonlyproteinfhl2reducesvascularlesionformationinvolvinginhibitionofproliferationandmigrationofsmoothmusclecells
AT lukascheukamp limonlyproteinfhl2reducesvascularlesionformationinvolvinginhibitionofproliferationandmigrationofsmoothmusclecells
AT janstap limonlyproteinfhl2reducesvascularlesionformationinvolvinginhibitionofproliferationandmigrationofsmoothmusclecells
AT viviandewaard limonlyproteinfhl2reducesvascularlesionformationinvolvinginhibitionofproliferationandmigrationofsmoothmusclecells
AT claudiamvantiel limonlyproteinfhl2reducesvascularlesionformationinvolvinginhibitionofproliferationandmigrationofsmoothmusclecells
AT carliejmdevries limonlyproteinfhl2reducesvascularlesionformationinvolvinginhibitionofproliferationandmigrationofsmoothmusclecells
_version_ 1718421849595969536