Kruppel-like factor 15 regulates smooth muscle response to vascular injury--brief report.
To determine the role of Kruppel-like factor (KLF) 15, a zinc finger transcriptional factor that is expressed in vascular smooth muscle cells (VSMCs) in vascular biology. VSMCs respond to mechanical injury via a tightly orchestrated series of gene regulatory events. KLF15 is broadly expressed in both arterial and venous vascular beds in a VSMC restricted fashion. KLF15 expression is markedly reduced by both pharmacological and mechanical stimuli. To examine the specific role of KLF15 in the vascular response to injury, we performed femoral artery wire injury in KLF15(-/-) and wild-type mice. KLF15(-/-) mice develop exaggerated neointimal growth, with evidence of increased SMC proliferation and migration within the neointima. In concordance, gain and loss of function studies in isolated VSMCs demonstrate that KLF15 can directly inhibit SMC proliferation and migration. To our knowledge, these data are the first to identify KLF15 as a novel inhibitor of VSMC proliferation and migration and to implicate this factor as a critical regulator of the vascular response to injury.
Case Cardiovascular Research Institute, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Yuan
Y
Lu
Saptarsi
S
Haldar
Kevin
K
Croce
Yunmei
Y
Wang
Mashashi
M
Sakuma
Toshifumi
T
Morooka
Baiqiu
B
Wang
Darwin
D
Jeyaraj
Susan J
SJ
Gray
Daniel I
DI
Simon
Mukesh K
MK
Jain
D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017539:Tunica Intima / Q000293:injuries / Q000378:metabolism* / Q000473:pathology
D004268:DNA-Binding Proteins; C467418:Klf15 protein, mouse; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors