Article Text

THE ROLE OF JAK–STAT3 SIGNALLING PATHWAY DURING FETAL LUNG DEVELOPMENT
  1. C Nogueira-Silva 1,
  2. S Nunes1,
  3. R S Moura1,
  4. J Correia-Pinto1
  1. 1Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal
  2. 2Department of Pediatrics, Hospital S Marcos, Braga, Portugal
  3. 3Division of Pediatric Surgery, Department of Pediatrics, Hospital S Joao, Porto, Portugal

Abstract

Background and Aim The process of lung development involves several effectors that exert its action via the JAK/STAT signalling pathway. The elucidation of the signalling pathways involved in lung development may lead to strategies to rescue pulmonary hypoplasia associated with a broad spectrum of human diseases. Our aim was thus to clarify the role of STAT3 during fetal lung development.

Materials and Methods The STAT3 expression pattern was assessed by immunohistochemistry. Rat lung explants were harvested at 13.5 days postconception and cultured during 4 days with piceatannol, an inhibitor of STAT3 phosphorylation (0, 0.01, 0.1, 1, 10, 20, 30 ng/ml). STAT3, MAPK (ERK1/2, JNK and p38) and PI3-AKT phosphorylation in explants was assessed by Western blot. Morphometric analysis was performed in all lung explants.

Results STAT3 was expressed by pulmonary endothelium during lung development. Higher doses of piceatannol inhibited the JAK/STAT3 pathway and decreased lung growth. However, lower doses of piceatannol induced an increase of STAT3 phosphorylation (accordingly previously described in the literature) and also increased lung growth. Moreover, Western blot demonstrated no difference on ERK1/2, JNK, p38 and PI3-AKT pathways.

Conclusions These findings suggest that the JAK/STAT3 signalling pathway is a positive regulator of fetal lung development. Moreover, the STAT3 endothelial expression proposes an airway–vasculature interaction on branching regulation.

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