PMID- 19690384
OWN - NLM
STAT- MEDLINE
DCOM- 20091002
LR  - 20211020
IS  - 1558-8238 (Electronic)
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 119
IP  - 9
DP  - 2009 Sep
TI  - Wnt signaling regulates smooth muscle precursor development in the mouse lung via 
      a tenascin C/PDGFR pathway.
PG  - 2538-49
LID - 38079 [pii]
LID - 10.1172/JCI38079 [doi]
AB  - Paracrine signaling from lung epithelium to the surrounding mesenchyme is 
      important for lung SMC development and function and is a contributing factor in 
      an array of pulmonary diseases such as bronchopulmonary dysplasia, pulmonary 
      hypertension, and asthma. Wnt7b, which is exclusively expressed in the lung 
      epithelium, is important for lung vascular smooth muscle integrity, but the 
      underlying mechanism by which Wnt signaling regulates lung SMC development is 
      unclear. In this report, we have demonstrated that Wnt7b regulates a program of 
      mesenchymal differentiation in the mouse lung that is essential for SMC 
      development. Genetic loss-of-function studies showed that Wnt7b and beta-catenin 
      were required for expression of Pdgfralpha and Pdgfrbeta and proliferation in 
      pulmonary SMC precursors. In contrast, gain-of-function studies showed that 
      activation of Wnt signaling increased the expression of both Pdgfralpha and 
      Pdgfrbeta as well as the proliferation of SMC precursors. We further showed that 
      the effect on Pdgfr expression was, in part, mediated by direct transcriptional 
      regulation of the ECM protein tenascin C (Tnc), which was necessary and 
      sufficient for Pdgfralpha/beta expression in lung explants. Moreover, this 
      pathway was highly upregulated in a mouse model of asthma and in lung tissue from 
      patients with pulmonary hypertension. Together, these data define a Wnt/Tnc/Pdgfr 
      signaling axis that is critical for smooth muscle development and disease 
      progression in the lung.
FAU - Cohen, Ethan David
AU  - Cohen ED
AD  - Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 
      19104, USA. cohene@mail.med.upenn.edu
FAU - Ihida-Stansbury, Kaori
AU  - Ihida-Stansbury K
FAU - Lu, Min Min
AU  - Lu MM
FAU - Panettieri, Reynold A
AU  - Panettieri RA
FAU - Jones, Peter Lloyd
AU  - Jones PL
FAU - Morrisey, Edward E
AU  - Morrisey EE
LA  - eng
GR  - R01 HL087825/HL/NHLBI NIH HHS/United States
GR  - P01 HL075215/HL/NHLBI NIH HHS/United States
GR  - HL079196/HL/NHLBI NIH HHS/United States
GR  - R01 HL079196/HL/NHLBI NIH HHS/United States
GR  - HL087528/HL/NHLBI NIH HHS/United States
GR  - HL087825/HL/NHLBI NIH HHS/United States
GR  - F32 HL087528/HL/NHLBI NIH HHS/United States
GR  - HL075215/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 - 20090817
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (CTNNB1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Tenascin)
RN  - 0 (Wnt Proteins)
RN  - 0 (Wnt7b protein, mouse)
RN  - 0 (beta Catenin)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor alpha)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta)
SB  - IM
MH  - Animals
MH  - Asthma/metabolism
MH  - Cell Proliferation
MH  - Embryonic Stem Cells/cytology/metabolism
MH  - Female
MH  - Humans
MH  - Hypertension, Pulmonary/metabolism
MH  - Lung/blood supply/cytology/*embryology/*metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Mutant Strains
MH  - Mice, Transgenic
MH  - Models, Biological
MH  - Myocytes, Smooth Muscle/cytology/*metabolism
MH  - Pregnancy
MH  - Proto-Oncogene Proteins/deficiency/genetics/*metabolism
MH  - Receptor, Platelet-Derived Growth Factor alpha/*metabolism
MH  - Receptor, Platelet-Derived Growth Factor beta/*metabolism
MH  - Signal Transduction
MH  - Tenascin/*metabolism
MH  - Wnt Proteins/deficiency/genetics/*metabolism
MH  - beta Catenin/deficiency/genetics/metabolism
PMC - PMC2735923
EDAT- 2009/08/20 09:00
MHDA- 2009/10/03 06:00
PMCR- 2009/08/17
CRDT- 2009/08/20 09:00
PHST- 2008/11/17 00:00 [received]
PHST- 2009/06/23 00:00 [accepted]
PHST- 2009/08/20 09:00 [entrez]
PHST- 2009/08/20 09:00 [pubmed]
PHST- 2009/10/03 06:00 [medline]
PHST- 2009/08/17 00:00 [pmc-release]
AID - 38079 [pii]
AID - 10.1172/JCI38079 [doi]
PST - ppublish
SO  - J Clin Invest. 2009 Sep;119(9):2538-49. doi: 10.1172/JCI38079. Epub 2009 Aug 17.