Inhibition of JNK enhances TGF-β1-activated Smad2 signaling in mouse embryonic lung

Shu Wu, Kalyani Kasisomayajula, Jinghong Peng, Eduardo Bancalari

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The Smad2/3 pathway plays a key role in mediating TGF-β1 inhibition of branching morphogenesis and induction of connective tissue growth factor (CTGF) expression in embryonic lungs. Because a number of cell-specific interactions have been described between TGF-β1-driven Smad signaling and the c-Jun N-terminal kinase (JNK) pathway, we have investigated the effects of JNK inhibition on TGF-β1 activation of Smad2, inhibition of branching, induction of CTGF expression, and apoptosis in mouse embryonic lung explants. Mouse embryonic day 12.5 (E12.5) lung explants were treated with TGF-β1 in the presence or absence of a specific pharmacologic JNK inhibitor (SP600125) and a specific JNK peptide inhibitor (JNKI). We found that TGF-β1 activated the JNK pathway by stimulating c-Jun phosphorylation, which was blocked by JNK inhibitors. Treatment with SP600125 stimulated Smad2 phosphorylation and enhanced TGF-β1-induced Smad2 phosphorylation. Treatment with JNK inhibitors also decreased normal branching morphogenesis and induced CTGF expression as well as augmented TGF-β1 inhibition of branching and induction of CTGF expression. Furthermore, JNK inhibition-induced apoptosis. Our results demonstrate that inhibition of the JNK pathway promotes TGF-β1-driven Smad2 responses in lung branching morphogenesis. These data suggest that the JNK pathway may antagonize TGF-β1 dependent Smad2 signaling during mouse embryonic lung development.

Original languageEnglish
Pages (from-to)381-386
Number of pages6
JournalPediatric Research
Volume65
Issue number4
DOIs
StatePublished - Apr 1 2009

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Phosphotransferases
Lung
Connective Tissue Growth Factor
Morphogenesis
Phosphorylation
Apoptosis
JNK Mitogen-Activated Protein Kinases
Cell Communication
Embryonic Development
Peptides

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Inhibition of JNK enhances TGF-β1-activated Smad2 signaling in mouse embryonic lung. / Wu, Shu; Kasisomayajula, Kalyani; Peng, Jinghong; Bancalari, Eduardo.

In: Pediatric Research, Vol. 65, No. 4, 01.04.2009, p. 381-386.

Research output: Contribution to journalArticle

Wu, Shu ; Kasisomayajula, Kalyani ; Peng, Jinghong ; Bancalari, Eduardo. / Inhibition of JNK enhances TGF-β1-activated Smad2 signaling in mouse embryonic lung. In: Pediatric Research. 2009 ; Vol. 65, No. 4. pp. 381-386.
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