Krüppel-like factor (KLF) 5 mediates cyclin D1 expression and cell proliferation via interaction with c-Jun in Ang II-induced VSMCs.
OBJECTIVE
To elucidate how krüppel-like factor (KLF5) activates cyclin D1 expression in Ang II-induced vascular smooth muscle cells (VSMC) proliferation.


METHODS
An adenoviral vector containing the full-length cDNA of KLF5 and a recombinant plasmid expressing c-Jun were constructed. MTT assay and flow cytometric analysis were used to determine the effect of Ang II on cell growth. The luciferase assay and chromatin immunoprecipitation were used to detect the relationship between KLF5 and c-Jun in transactivation of cyclin D1 gene expression.


RESULTS
Ang II upregulated the expression of KLF5 with concurrent acceleration of the cell cycle progression in VSMCs. Ang II induced KLF5 activation via the ERK and p38 MAPK pathways triggered by AT-1 receptor. High DNA binding activity and functional interaction of KLF5 and c-Jun were found in Ang II-induced VSMCs. Cotransfection of KLF5 and c-Jun expression vectors significantly increased cyclin D1 promoter activity.


CONCLUSIONS
KLF5 is a downstream signal of the ERK 1/2 and p38 MAPK pathways, and activates the transcription of cyclin D1 gene via functional interaction with c-Jun in Ang II-induced VSMC proliferation.
Liu
Yu
Y
Department of Biochemistry and Molecular Biology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China.
Wen
Jin-kun
JK
Dong
Li-hua
LH
Zheng
Bin
B
Han
Mei
M
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014158:Transcription, Genetic; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C492215:Klf5 protein, rat; D051741:Kruppel-Like Transcription Factors; D016755:Proto-Oncogene Proteins c-jun; D000804:Angiotensin II; D019938:Cyclin D1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases