Acta Pharmacologica Sinica (2010) 31: 10–18; doi: 10.1038/aps.2009.185; published online 28 December 2009

Aim: 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. 

Conclusion: 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.

Keywords: Krüppel-like factor 5; cyclin D1; angiotensin II; proliferation; vascular smooth muscle cells