PMID- 28582407
OWN - NLM
STAT- MEDLINE
DCOM- 20170918
LR  - 20200310
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 6
DP  - 2017
TI  - Enhanced expression and phosphorylation of Sirt7 activates smad2 and ERK 
      signaling and promotes the cardiac fibrosis differentiation upon angiotensin-II 
      stimulation.
PG  - e0178530
LID - 10.1371/journal.pone.0178530 [doi]
LID - e0178530
AB  - Cardiac fibroblasts (CFs) phenotypic conversion to myofibroblasts (MFs) 
      represents a crucial event in cardiac fibrosis that leads to impaired cardiac 
      function. However, regulation of this phenotypic transformation remains unclear. 
      Here, we showed that sirtuin-7 (Sirt7) plays an important role in the regulation 
      of MFs differentiation. Sirt7 expression and phosphorylation were upregulated in 
      CFs upon angiotensin-II (Ang-II) stimulation. Sirt7 depletion by siRNA in CFs 
      resulted in decreased cell proliferation and extracellular matrix (ECM) 
      deposition. Further, examination of Sirt7-depleted CFs demonstrated significantly 
      lower expression of alpha-smooth muscle actin (alpha-SMA), the classical marker of MFs 
      differentiation, and decreased formation of focal adhesions. Moreover, 
      overexpression of Sirt7 increased alpha-SMA expression in Ang-II treated CFs and 
      exacerbated Ang-II-induced MFs differentiation. Moreover, Sirt7 depletion could 
      largely reverse Ang-II induced increase of nuclear translocalization and activity 
      of smad2 and extracellular regulated kinases (ERK) in CFs. Importantly, the 
      increased differentiation of CFs to MFs was also abolished by smad2 siRNA or 
      U0126. Our findings reveal a novel role of Sirt7 and its phosphorylation in the 
      phenotypic conversion of CFs to MFs and might lead to the development of new 
      therapeutic and prognostic tools for cardiac fibrosis.
FAU - Wang, Haichen
AU  - Wang H
AD  - Department of Cardiovascular Surgery, First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an, Shaanxi, China.
FAU - Liu, Shengwu
AU  - Liu S
AD  - Department of Neurology, Affiliated Hospital of Yan'an University, Yan'an, 
      Shaanxi, China.
FAU - Liu, Shengqiang
AU  - Liu S
AD  - Department of Cardiology, Ankang Central Hospital, Ankang, Shaanxi, China.
FAU - Wei, Wei
AU  - Wei W
AD  - Department of Neurosurgery, Affiliated Hospital of Yan'an University, Yan'an, 
      Shaanxi, China.
FAU - Zhou, Xiaolong
AU  - Zhou X
AD  - Department of Neurosurgery, Baoji Central Hospital, Baoji, Shaanxi, China.
FAU - Lin, Fang
AU  - Lin F
AD  - Department of Geriatrics, Affiliated Hospital of Yan'an University, Yan'an, 
      Shaanxi, China.
FAU - Wang, Juanjuan
AU  - Wang J
AD  - Department of Neurology, Affiliated Hospital of Yan'an University, Yan'an, 
      Shaanxi, China.
FAU - Chen, Jinye
AU  - Chen J
AD  - Department of Cardiovascular and Pulmonary, Ankang Central Hospital, Ankang, 
      Shaanxi, China.
FAU - Zhang, Guodong
AU  - Zhang G
AD  - Department of Brain Tumor, Baoji Central Hospital, Baoji, Shaanxi, China.
FAU - Pang, Yongbing
AU  - Pang Y
AD  - Department of Neurosurgery, Affiliated Hospital of Yan'an University, Yan'an, 
      Shaanxi, China.
LA  - eng
PT  - Journal Article
DEP - 20170605
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Actins)
RN  - 0 (Butadienes)
RN  - 0 (Nitriles)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (SIRT7 protein, rat)
RN  - 0 (Smad2 Protein)
RN  - 0 (Smad2 protein, rat)
RN  - 0 (U 0126)
RN  - 0 (smooth muscle actin, rat)
RN  - 11128-99-7 (Angiotensin II)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 3.5.1.- (Sirtuins)
SB  - IM
MH  - Actins/genetics/metabolism
MH  - Angiotensin II/*pharmacology
MH  - Animals
MH  - Butadienes/pharmacology
MH  - Cell Differentiation/drug effects
MH  - Cell Proliferation
MH  - Extracellular Matrix/drug effects/metabolism
MH  - Fibroblasts/cytology/*drug effects/metabolism
MH  - Focal Adhesions/drug effects/metabolism
MH  - Gene Expression Regulation
MH  - Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/genetics/metabolism
MH  - Mitogen-Activated Protein Kinase 3/antagonists & inhibitors/genetics/metabolism
MH  - Myocardium/cytology/metabolism
MH  - Myofibroblasts/cytology/*drug effects/metabolism
MH  - Nitriles/pharmacology
MH  - Phosphorylation/drug effects
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Protein Transport
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Rats
MH  - Signal Transduction
MH  - Sirtuins/antagonists & inhibitors/*genetics/metabolism
MH  - Smad2 Protein/agonists/*genetics/metabolism
PMC - PMC5459426
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2017/06/06 06:00
MHDA- 2017/09/19 06:00
PMCR- 2017/06/05
CRDT- 2017/06/06 06:00
PHST- 2017/01/23 00:00 [received]
PHST- 2017/05/15 00:00 [accepted]
PHST- 2017/06/06 06:00 [entrez]
PHST- 2017/06/06 06:00 [pubmed]
PHST- 2017/09/19 06:00 [medline]
PHST- 2017/06/05 00:00 [pmc-release]
AID - PONE-D-17-02964 [pii]
AID - 10.1371/journal.pone.0178530 [doi]
PST - epublish
SO  - PLoS One. 2017 Jun 5;12(6):e0178530. doi: 10.1371/journal.pone.0178530. 
      eCollection 2017.