Kurakula, Kondababu, Vos, Mariska, Rubio, Iker Otermin, Marinkovic, Goran ORCID: 0000-0002-3581-9900, Buettner, Reinhard, Heukamp, Lukas C., Stap, Jan, de Waard, Vivian, van Tiel, Claudia M. and de Vries, Carlie J. M. (2014). The LIM-Only Protein FHL2 Reduces Vascular Lesion Formation Involving Inhibition of Proliferation and Migration of Smooth Muscle Cells. PLoS One, 9 (4). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Kurakula, KondababuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vos, MariskaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rubio, Iker OterminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marinkovic, GoranUNSPECIFIEDorcid.org/0000-0002-3581-9900UNSPECIFIED
Buettner, ReinhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heukamp, Lukas C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stap, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Waard, VivianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Tiel, Claudia M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Vries, Carlie J. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-440642
DOI: 10.1371/journal.pone.0094931
Journal or Publication Title: PLoS One
Volume: 9
Number: 4
Date: 2014
Publisher: PUBLIC LIBRARY SCIENCE
Place of Publication: SAN FRANCISCO
ISSN: 1932-6203
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NUCLEAR RECEPTOR NUR77; DOMAIN PROTEIN-2; STENT RESTENOSIS; BLOOD-FLOW; CYCLIN D1; ATHEROSCLEROSIS; ACTIVATION; DISEASE; TARGET; ARTERYMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/44064

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