RGD Reference Report - KLF5/BTEB2, a Kruppel-like zinc-finger type transcription factor, mediates both smooth muscle cell activation and cardiac hypertrophy. - Rat Genome Database

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KLF5/BTEB2, a Kruppel-like zinc-finger type transcription factor, mediates both smooth muscle cell activation and cardiac hypertrophy.

Authors: Nagai, R  Shindo, T  Manabe, I  Suzuki, T  Kurabayashi, M 
Citation: Nagai R, etal., Adv Exp Med Biol 2003;538:57-65; discussion 66.
RGD ID: 1304323
Pubmed: PMID:15098654   (View Abstract at PubMed)

Cardiac and vascular biology need to be approached interactively because they share many common biological features as seen in activation of the local renin-angiotensin system, angiogenesis, and extracellular matrix production. We previously reported KLF5/BTEB2, a Kruppel-like zinc-finger type transcription factor, to activate various gene promoters that are activated in phenotypically modulated smooth muscle cells, such as a nonmuscle type myosin heavy chain gene SMemb, plasminogen activator inhibitor-1 (PAI-1), iNOS, PDGF-A, Egr-1 and VEGF receptors at least in vitro. KLF5/BTEB2 mRNA levels are downregulated with vascular development but upregulated in neointima that is produced in response to vascular injury. Mitogenic stimulation activates KLF5/BTEB2 gene expression through MEK1 and Egr-1. Chromatin immunoprecipitation assay showed KLF5/BTEB2 to be induced and to bind the promoter of the PDGF-A gene in response to angiotensin II stimulation. In order to define the role of KLF5/BTEB2 in cardiovascular remodeling, we targeted the KLF5/BTEB2 gene in mice. Homozygous mice resulted in early embryonic lethality whereas heterozygous mice were apparently normal. However, in response to external stress, arteries of heterozygotes exhibited diminished levels of smooth muscle and adventitial cell activation. Furthermore, cardiac fibrosis and hypertrophy induced by continuous angiotensin II infusion. We also found that RARa binds KLF5/BTEB2, and that Am80, a potent synthetic RAR agonist, inhibits angiotensin II-induced cardiac hypertrophy. These results indicate that KLF5/BTEB2 is an essential transcription factor that causes not only smooth muscle phenotypic modulation but also cardiac hypertrophy and fibrosis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Cardiomegaly  ISOKlf5 (Mus musculus)1304323; 1304323 RGD 
Cardiomegaly  IMP 1304323 RGD 
Fibrosis severityISOKlf5 (Mus musculus)1304323; 1304323 RGD 
Fibrosis severityIMP 1304323 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Klf5  (KLF transcription factor 5)

Genes (Mus musculus)
Klf5  (Kruppel-like transcription factor 5)

Genes (Homo sapiens)
KLF5  (KLF transcription factor 5)

Objects referenced in this article
Gene KDR kinase insert domain receptor Homo sapiens
Gene Kdr kinase insert domain protein receptor Mus musculus
Gene Kdr kinase insert domain receptor Rattus norvegicus

Additional Information