PMID- 23646205
OWN - NLM
STAT- MEDLINE
DCOM- 20131126
LR  - 20211203
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 4
DP  - 2013
TI  - Kruppel-like factor 4 transcriptionally regulates TGF-beta1 and contributes to 
      cardiac myofibroblast differentiation.
PG  - e63424
LID - 10.1371/journal.pone.0063424 [doi]
LID - e63424
AB  - Angiotensin II (Ang II) plays a major role in the pathogenesis of cardiac 
      fibrosis in hypertension. It is known that Ang II induces TGF-beta1 expression. How 
      transcription mediates Ang II-induced TGF-beta1 expression, as well as its 
      contribution to cardiac fibrosis, is unknown. We studied the role of Kruppel-like 
      family transcription factors in Ang II-induced myofibroblast formation. We found 
      that among the Kruppel-like family members, Kruppel-like factor 4 (Klf4) was the 
      highest expressed form in isolated cardiac fibroblasts after Ang II treatment. 
      Klf4 increased expression of alpha-SMA and collagen, as well as increased 
      myofibroblast formation. ChIP assays showed that Klf4 specifically bound to the 
      TGF-beta1 promoter. Deletion and mutagenesis analysis showed that the sites at 
      -184 approximately -180 bp and -45 approximately -41 bp in the TGF-beta1 promoter were responsible for Klf4 
      transactivation of the TGF-beta1 promoter. Our studies demonstrate that Klf4 plays a 
      pivotal role in Ang II-induced cardiac myofibroblast differentiation and collagen 
      synthesis through transcriptional upregulation of TGF-beta1.
FAU - Zhang, Yi
AU  - Zhang Y
AD  - Beijing Anzhen Hospital, Capital Medical University, The Key Laboratory of 
      Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 
      Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.
FAU - Wang, Ying
AU  - Wang Y
FAU - Liu, Yan
AU  - Liu Y
FAU - Wang, Nanping
AU  - Wang N
FAU - Qi, Yongfen
AU  - Qi Y
FAU - Du, Jie
AU  - Du J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130430
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Klf4 protein, mouse)
RN  - 0 (Kruppel-Like Factor 4)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 11128-99-7 (Angiotensin II)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Angiotensin II/administration & dosage
MH  - Animals
MH  - Cell Differentiation/drug effects/*genetics
MH  - Collagen/biosynthesis
MH  - Fibroblasts/drug effects/metabolism
MH  - *Gene Expression Regulation/drug effects
MH  - Kruppel-Like Factor 4
MH  - Kruppel-Like Transcription Factors/genetics/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Myoblasts, Cardiac/*cytology/*metabolism
MH  - Myocardium/metabolism
MH  - Myofibroblasts/*cytology/*metabolism
MH  - Promoter Regions, Genetic
MH  - Transcriptional Activation
MH  - Transforming Growth Factor beta1/*genetics/metabolism
PMC - PMC3640021
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/05/07 06:00
MHDA- 2013/12/16 06:00
PMCR- 2013/04/30
CRDT- 2013/05/07 06:00
PHST- 2013/02/21 00:00 [received]
PHST- 2013/03/30 00:00 [accepted]
PHST- 2013/05/07 06:00 [entrez]
PHST- 2013/05/07 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
PHST- 2013/04/30 00:00 [pmc-release]
AID - PONE-D-13-07793 [pii]
AID - 10.1371/journal.pone.0063424 [doi]
PST - epublish
SO  - PLoS One. 2013 Apr 30;8(4):e63424. doi: 10.1371/journal.pone.0063424. Print 2013.