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Title: Modulation of Cardiac Fibrosis by Krüppel-like Factor 6 through Transcriptional Control of Thrombospondin 4 in Cardiomyocytes.
Authors: Sawaki, D.
Hou, L.
Tomida, S.
Sun, J.
Zhan, H.
Aizawa, K.
Son, B. K.
Kariya, T.
Takimoto, E.
Otsu, K.
Conway, S. J.
Manabe, I.
Komuro, I.
Friedman, S. L.
Nagai, R.
Suzuki, Toru
First Published: 18-May-2015
Publisher: Oxford University Press (OUP) for European Society of Cardiology
Citation: Cardiovascular Research, 2015
Abstract: Aims: Krüppel-like factors (KLFs) are a family of transcription factors which play important roles in the heart under pathological and developmental conditions. We previously identified and cloned Klf6whose homozygous mutation in mice results in embryonic lethality suggesting a role in cardiovascular development. Effects of KLF6 on pathologic regulation of the heart were investigated in the present study. Methods and Results Mice heterozygous for Klf6resulted in significantly diminished levels of cardiac fibrosis in response to angiotensin II infusion. Intriguingly, a similar phenotype was seen in cardiomyocyte-specific Klf6knockout mice but not in cardiac fibroblast-specific knockout mice. Microarray analysis revealed increased levels of the extra-cellular matrix factor, thrombospondin 4 (TSP4), in Klf6-ablated heart. Mechanistically, KLF6 directly suppressed Tsp4expression levels, and cardiac TSP4 regulated the activation of cardiac fibroblasts to regulate cardiac fibrosis. Conclusion Our present studies on the cardiac function of KLF6 show a new mechanism whereby cardiomyocytes regulate cardiac fibrosis through transcriptional control of the extra-cellular matrix factor, TSP4, which in turn, modulates activation of cardiac fibroblasts.
DOI Link: 10.1093/cvr/cvv155
ISSN: 0008-6363
eISSN: 1755-3245
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Archived with reference to SHERPA/RoMEO and publisher website. This is a pre-copyedited, author-produced PDF of an article accepted for publication in Cardiovascular Research following peer review. The version of record Cardiovascular Research 2015 is available online at:
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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