PMID- 20890045
OWN - NLM
STAT- MEDLINE
DCOM- 20101110
LR  - 20211020
IS  - 1558-8238 (Electronic)
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 120
IP  - 10
DP  - 2010 Oct
TI  - Proapoptotic Rassf1A/Mst1 signaling in cardiac fibroblasts is protective against 
      pressure overload in mice.
PG  - 3555-67
LID - 43569 [pii]
LID - 10.1172/JCI43569 [doi]
AB  - Mammalian sterile 20-like kinase 1 (Mst1) is a mammalian homolog of Drosophila 
      Hippo, the master regulator of cell death, proliferation, and organ size in 
      flies. It is the chief component of the mammalian Hippo pathway and promotes 
      apoptosis and inhibits compensatory cardiac hypertrophy, playing a critical role 
      in mediating heart failure. How Mst1 is regulated, however, remains unclear. 
      Using genetically altered mice in which expression of the tumor suppressor 
      Ras-association domain family 1 isoform A (Rassf1A) was modulated in a cell 
      type-specific manner, we demonstrate here that Rassf1A is an endogenous activator 
      of Mst1 in the heart. Although the Rassf1A/Mst1 pathway promoted apoptosis in 
      cardiomyocytes, thereby playing a detrimental role, the same pathway surprisingly 
      inhibited fibroblast proliferation and cardiac hypertrophy through both 
      cell-autonomous and autocrine/paracrine mechanisms, playing a protective role 
      during pressure overload. In cardiac fibroblasts, the Rassf1A/Mst1 pathway 
      negatively regulated TNF-alpha, a key mediator of hypertrophy, fibrosis, and 
      resulting cardiac dysfunction. These results suggest that the functional 
      consequence of activating the proapoptotic Rassf1A/Mst1 pathway during pressure 
      overload is cell type dependent in the heart and that suppressing this mechanism 
      in cardiac fibroblasts could be detrimental.
FAU - Del Re, Dominic P
AU  - Del Re DP
AD  - Department of Cell Biology and Molecular Medicine, Cardiovascular Research 
      Institute, New Jersey Medical School, University of Medicine and Dentistry of New 
      Jersey, Newark, New Jersey 07103-2714, USA.
FAU - Matsuda, Takahisa
AU  - Matsuda T
FAU - Zhai, Peiyong
AU  - Zhai P
FAU - Gao, Shumin
AU  - Gao S
FAU - Clark, Geoffrey J
AU  - Clark GJ
FAU - Van Der Weyden, Louise
AU  - Van Der Weyden L
FAU - Sadoshima, Junichi
AU  - Sadoshima J
LA  - eng
GR  - HL67724/HL/NHLBI NIH HHS/United States
GR  - R01 HL091469/HL/NHLBI NIH HHS/United States
GR  - P01 AG027211/AG/NIA NIH HHS/United States
GR  - HL69020/HL/NHLBI NIH HHS/United States
GR  - F32 HL099148/HL/NHLBI NIH HHS/United States
GR  - R01 HL067724/HL/NHLBI NIH HHS/United States
GR  - P01 HL059139/HL/NHLBI NIH HHS/United States
GR  - R01 AG023039/AG/NIA NIH HHS/United States
GR  - AG27211/AG/NIA NIH HHS/United States
GR  - R01 HL102738/HL/NHLBI NIH HHS/United States
GR  - HL099148/HL/NHLBI NIH HHS/United States
GR  - HL91469/HL/NHLBI NIH HHS/United States
GR  - P01 HL069020/HL/NHLBI NIH HHS/United States
GR  - HL59139/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100920
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (NF-kappa B)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RASSF1 protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (macrophage stimulating protein)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
SB  - IM
MH  - Animals
MH  - Blood Pressure
MH  - Cells, Cultured
MH  - Fibroblasts/metabolism/pathology
MH  - Hepatocyte Growth Factor/*physiology
MH  - Mice
MH  - Myocytes, Cardiac/*metabolism/pathology
MH  - NF-kappa B/antagonists & inhibitors
MH  - Proto-Oncogene Proteins/*physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Signal Transduction/*physiology
MH  - Stress, Physiological
MH  - Tumor Necrosis Factor-alpha/genetics
MH  - Tumor Suppressor Proteins/*physiology
PMC - PMC2947240
EDAT- 2010/10/05 06:00
MHDA- 2010/11/11 06:00
PMCR- 2010/09/20
CRDT- 2010/10/05 06:00
PHST- 2010/05/02 00:00 [received]
PHST- 2010/08/09 00:00 [accepted]
PHST- 2010/10/05 06:00 [entrez]
PHST- 2010/10/05 06:00 [pubmed]
PHST- 2010/11/11 06:00 [medline]
PHST- 2010/09/20 00:00 [pmc-release]
AID - 43569 [pii]
AID - 10.1172/JCI43569 [doi]
PST - ppublish
SO  - J Clin Invest. 2010 Oct;120(10):3555-67. doi: 10.1172/JCI43569. Epub 2010 Sep 20.