scholarly journals TGF-β1 inhibits the apoptosis of pulmonary arterial smooth muscle cells and contributes to pulmonary vascular medial thickening via the PI3K/Akt pathway

2016 ◽  
Vol 13 (3) ◽  
pp. 2751-2756 ◽  
Author(s):  
LIMIN LI ◽  
XIAOQIAN ZHANG ◽  
XIAOXIA LI ◽  
CHENGFANG LV ◽  
HONGJUAN YU ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Akt Pathway ◽  
Arterial Smooth Muscle ◽  
Pulmonary Arterial ◽  
Arterial Smooth Muscle Cells ◽  
Pulmonary Arterial Smooth Muscle ◽  
Medial Thickening ◽  
Tgf Β1

ANP signaling inhibits TGF-β-induced Smad2 and Smad3 nuclear translocation and extracellular matrix expression in rat pulmonary arterial smooth muscle cells

2007 ◽  
Vol 102 (1) ◽  
pp. 390-398 ◽  
Author(s):  
Peng Li ◽  
Suzanne Oparil ◽  
Lea Novak ◽  
Xu Cao ◽  
Weibin Shi ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Nuclear Translocation ◽  
Muscle Cells ◽  
Arterial Smooth Muscle ◽  
Pulmonary Arterial ◽  
Arterial Smooth Muscle Cells ◽  
Pulmonary Arterial Smooth Muscle ◽  
Tgf Β1

Atrial natriuretic peptide (ANP) and transforming growth factor (TGF)-β play important counterregulatory roles in pulmonary vascular adaptation to chronic hypoxia. To define the molecular mechanism of this important interaction, we tested whether ANP-cGMP-protein kinase G (PKG) signaling inhibits TGF-β1-induced extracellular matrix (ECM) expression and defined the specific site(s) at which this molecular merging of signaling pathways occurs. Rat pulmonary arterial smooth muscle cells (PASMCs) were treated with ANP (1 μM) or cGMP (1 mM) with or without pretreatment with PKG inhibitors KT-5823 (1 μM) or Rp-8-bromo-cGMP (Rp-8-Br-cGMP 50 μM), then exposed to TGF-β1 (1 ng/ml) for 5–360 min (for pSmad nuclear translocation and protein analysis) or 24 h (for ECM mRNA expression). Nuclear translocation of pSmad2 and pSmad3 was assessed by fluorescent confocal microscopy. ANP and cGMP inhibited TGF-β1-induced pSmad2 and pSmad3 nuclear translocation and expression of periostin, osteopontin, and plasminogen activator inhibitor-1 mRNA and protein, but not TGF-β1-induced phosphorylation of Smad2 and Smad3. KT-5823 and Rp-8-Br-cGMP blocked ANP/cGMP-induced activation of PKG and inhibition of TGF-β1-stimulated nuclear translocation of pSmad2 and pSmad3 in PASMCs. These results reveal for the first time a precise site at which ANP-cGMP-PKG signaling exerts its antifibrogenic effect on the profibrogenic TGF-β1 signaling pathway: by blocking TGF-β1-induced pSmad2 and pSmad3 nuclear translocation and ECM expression in PASMCs. Blocking nuclear translocation and subsequent binding of pSmad2 and pSmad3 to TGF-β-Smad response elements in ECM genes may be responsible for the inhibitory effects of ANP on TGF-β-induced expression of ECM molecules.

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