PMID- 17322285
OWN - NLM
STAT- MEDLINE
DCOM- 20070727
LR  - 20200930
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 292
IP  - 6
DP  - 2007 Jun
TI  - Modulation of pulmonary vascular smooth muscle cell phenotype in hypoxia: role of 
      cGMP-dependent protein kinase.
PG  - L1459-66
AB  - Chronic hypoxia triggers pulmonary vascular remodeling, which is associated with 
      a modulation of the vascular smooth muscle cell (SMC) phenotype from a 
      contractile, differentiated to a synthetic, dedifferentiated state. We previously 
      reported that acute hypoxia represses cGMP-dependent protein kinase (PKG) 
      expression in ovine fetal pulmonary venous SMCs (FPVSMCs). Therefore, we tested 
      if altered expression of PKG could explain SMC phenotype modulation after 
      exposure to hypoxia. Hypoxia-induced reduction in PKG protein expression strongly 
      correlated with the repressed expression of SMC phenotype markers, myosin heavy 
      chain (MHC), calponin, vimentin, alpha-smooth muscle actin (alphaSMA), and 
      thrombospondin (TSP), indicating that hypoxic exposure of SMC induced phenotype 
      modulation to dedifferentiated state, and PKG may be involved in SMC phenotype 
      modulation. PKG-specific small interfering RNA (siRNA) transfection in FPVSMCs 
      significantly attenuated calponin, vimentin, and MHC expression, with no effect 
      on alphaSMA and TSP. Treatment with 30 microM Drosophila Antennapedia (DT-3), a 
      membrane-permeable peptide inhibitor of PKG, attenuated the expression of TSP, 
      MHC, alphaSMA, vimentin, and calponin. The results from PKG siRNA and DT-3 
      studies indicate that hypoxia-induced reduction in protein expression was also 
      similarly impacted by PKG inhibition. Overexpression of PKG in FPVSMCs by 
      transfection with a full-length PKG construct tagged with green fluorescent 
      fusion protein (PKG-GFP) reversed the effect of hypoxia on the expression of SMC 
      phenotype marker proteins. These results suggest that PKG could be one of the 
      determinants for the expression of SMC phenotype marker proteins and may be 
      involved in the maintenance of the differentiated phenotype in pulmonary vascular 
      SMCs in hypoxia.
FAU - Zhou, Weilin
AU  - Zhou W
AD  - Division of Neonatology, Harbor-UCLA Medical Center, Los Angeles Biomedical 
      Research Institute at Harbor-UCLA, 1124 West Carson St., Torrance, CA 90502, USA. 
      wzhou@labiomed.org
FAU - Dasgupta, Chiranjib
AU  - Dasgupta C
FAU - Negash, Sewite
AU  - Negash S
FAU - Raj, J Usha
AU  - Raj JU
LA  - eng
GR  - HL-59435/HL/NHLBI NIH HHS/United States
GR  - HL-75187/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070223
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Biomarkers)
RN  - 0 (RNA, Small Interfering)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 2.7.11.12 (Cyclic GMP-Dependent Protein Kinases)
SB  - IM
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Cells, Cultured
MH  - Cyclic GMP-Dependent Protein Kinases/genetics/*metabolism
MH  - Down-Regulation/physiology
MH  - Female
MH  - Gene Expression Regulation, Enzymologic
MH  - Green Fluorescent Proteins/genetics
MH  - Hypoxia/*metabolism
MH  - Muscle, Smooth, Vascular/cytology/*enzymology
MH  - Phenotype
MH  - Pregnancy
MH  - Pulmonary Veins/cytology/*enzymology
MH  - RNA, Small Interfering
MH  - Sheep
MH  - Transfection
EDAT- 2007/02/27 09:00
MHDA- 2007/07/28 09:00
CRDT- 2007/02/27 09:00
PHST- 2007/02/27 09:00 [pubmed]
PHST- 2007/07/28 09:00 [medline]
PHST- 2007/02/27 09:00 [entrez]
AID - 00143.2006 [pii]
AID - 10.1152/ajplung.00143.2006 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2007 Jun;292(6):L1459-66. doi: 
      10.1152/ajplung.00143.2006. Epub 2007 Feb 23.