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PMID:12101409

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Citation

Shindo, T, Manabe, I, Fukushima, Y, Tobe, K, Aizawa, K, Miyamoto, S, Kawai-Kowase, K, Moriyama, N, Imai, Y, Kawakami, H, Nishimatsu, H, Ishikawa, T, Suzuki, T, Morita, H, Maemura, K, Sata, M, Hirata, Y, Komukai, M, Kagechika, H, Kadowaki, T, Kurabayashi, M and Nagai, R (2002) Krüppel-like zinc-finger transcription factor KLF5/BTEB2 is a target for angiotensin II signaling and an essential regulator of cardiovascular remodeling. Nat. Med. 8:856-63

Abstract

We recently isolated a Krüppel-like zinc-finger transcription factor 5 (KLF5; also known as BTEB2 and IKLF), which is markedly induced in activated vascular smooth-muscle cells and fibroblasts. Here we describe our analysis of the in vivo function of KLF5 using heterozygous KLF5-knockout mice (Klf5(+/-)). In response to external stress, Klf5(+/-) mice showed diminished levels of arterial-wall thickening, angiogenesis, cardiac hypertrophy and interstitial fibrosis. Also, angiotensin II induced expression of KLF5, which in turn activated platelet-derived growth factor-A (PDGF-A) and transforming growth factor-beta (TGF-beta) expression. In addition, we determined that KLF5 interacted with the retinoic-acid receptor (RAR), that synthetic RAR ligands modulated KLF5 transcriptional activity, and that in vivo administration of RAR ligands affected stress responses in the cardiovascular system in a KLF5-dependent manner. KLF5 thus seems to be a key element linking external stress and cardiovascular remodeling.

Links

PubMed Online version:10.1038/nm738

Keywords

Angiotensin II/metabolism; Angiotensin II/pharmacology; Animals; Blood Vessels/cytology; Blood Vessels/drug effects; Blood Vessels/metabolism; Cells, Cultured; Collagen Type IV/metabolism; Dibenzazepines/pharmacology; Digestive System/anatomy & histology; Digestive System Physiological Phenomena; Female; Genes, Reporter; Humans; Kruppel-Like Transcription Factors; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium/cytology; Myocardium/metabolism; Neoplasm Transplantation; Neovascularization, Physiologic; Platelet-Derived Growth Factor/genetics; Platelet-Derived Growth Factor/metabolism; Rats; Recombinant Fusion Proteins/metabolism; Retinoids/antagonists & inhibitors; Signal Transduction/physiology; Trans-Activators/genetics; Trans-Activators/metabolism; Ventricular Remodeling/physiology; Zinc Fingers

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:B1AVK5

part_of

GO:0005587: collagen type IV trimer

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:F7CK55

part_of

GO:0005587: collagen type IV trimer

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CO4A1

part_of

GO:0005587: collagen type IV trimer

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CO4A2

part_of

GO:0005587: collagen type IV trimer

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:RARA

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q9Z0Z7

F

Seeded From UniProt

complete

MOUSE:RARA

acts_upstream_of_or_within

GO:0006355: regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PDGFA

located_in

GO:0005902: microvillus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:P70165

part_of

GO:0005587: collagen type IV trimer

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:Q3TNM7

part_of

GO:0005587: collagen type IV trimer

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:Q3TP61

part_of

GO:0005587: collagen type IV trimer

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:Q61436

part_of

GO:0005587: collagen type IV trimer

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:Q63ZW6

part_of

GO:0005587: collagen type IV trimer

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:Q6PFB1

part_of

GO:0005587: collagen type IV trimer

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:Q80V57

part_of

GO:0005587: collagen type IV trimer

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:Q8BNS7

part_of

GO:0005587: collagen type IV trimer

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:Q9ESQ1

part_of

GO:0005587: collagen type IV trimer

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:Q9ESQ2

part_of

GO:0005587: collagen type IV trimer

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CO4A3

part_of

GO:0005587: collagen type IV trimer

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:KLF5

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P11416

F

Seeded From UniProt

complete

MOUSE:KLF5

acts_upstream_of

GO:0030033: microvillus assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3038696

P

Seeded From UniProt

complete

MOUSE:KLF5

acts_upstream_of_or_within

GO:0001525: angiogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3038696

P

Seeded From UniProt

complete

MOUSE:KLF5

enables

GO:0003677: DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:KLF5

enables

GO:0003700: DNA-binding transcription factor activity

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3038696

F

Seeded From UniProt

complete

MOUSE:KLF5

acts_upstream_of_or_within

GO:0045893: positive regulation of transcription, DNA-templated

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3038696

P

Seeded From UniProt

complete

MOUSE:PDGFA

acts_upstream_of_or_within

GO:0001525: angiogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PDGFA

part_of

GO:0005902: microvillus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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