High tidal volume ventilation activates Smad2 and upregulates expression of connective tissue growth factor in newborn rat lung

Shu Wu, Letizia Capasso, Andrea Lessa, Jinghong Peng, Kalyani Kasisomayajula, Maria Rodriguez, Cleide Suguihara, Eduardo Bancalari

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

High tidal volume (VT) ventilation plays a key role in ventilator induced lung injury and bronchopulmonary dysplasia. However, little is known about the effect of high VT on expression of growth factors that are critical to lung development. In a previous study, we demonstrated that connective tissue growth factor (CTGF) inhibits branching morphogenesis. In this study, we investigated the effect of high VT on CTGF expression in newborn rat lungs. Newborn rats were ventilated with normal VT (10 mL/kg) or high VT (25 mL/kg) for 6 h. Nonventilated animals served as controls. We found that high VT upregulated CTGF expression. To identify the potential signaling pathways mediating high VT induction of CTGF, newborn rats were ventilated with high VT for 1 or 3 h. Temporal expression of TGF-βs, p-Smad2, Smad7, and CTGF was analyzed. High VT ventilation did not change gene expression of TGF-βs and Smad7 but induced rapid and sustained expression of p-Smad2 that precedes increased CTGF expression. CTGF and p-Smad2 were localized in bronchiolar epithelial cells, alveolar walls and septa. These data suggest that high Vt ventilation activates the Smad2 pathway, which may be responsible for downstream induction of CTGF expression in newborn rat lungs.

Original languageEnglish
Pages (from-to)245-250
Number of pages6
JournalPediatric Research
Volume63
Issue number3
DOIs
StatePublished - Mar 1 2008

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Connective Tissue Growth Factor
Tidal Volume
Up-Regulation
Lung
Ventilation
Ventilator-Induced Lung Injury
Bronchopulmonary Dysplasia
Morphogenesis
Cell Wall
Intercellular Signaling Peptides and Proteins
Epithelial Cells
Gene Expression

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

High tidal volume ventilation activates Smad2 and upregulates expression of connective tissue growth factor in newborn rat lung. / Wu, Shu; Capasso, Letizia; Lessa, Andrea; Peng, Jinghong; Kasisomayajula, Kalyani; Rodriguez, Maria; Suguihara, Cleide; Bancalari, Eduardo.

In: Pediatric Research, Vol. 63, No. 3, 01.03.2008, p. 245-250.

Research output: Contribution to journalArticle

Wu, Shu ; Capasso, Letizia ; Lessa, Andrea ; Peng, Jinghong ; Kasisomayajula, Kalyani ; Rodriguez, Maria ; Suguihara, Cleide ; Bancalari, Eduardo. / High tidal volume ventilation activates Smad2 and upregulates expression of connective tissue growth factor in newborn rat lung. In: Pediatric Research. 2008 ; Vol. 63, No. 3. pp. 245-250.
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