Oxygen, gastrin-releasing Peptide, and pediatric lung disease: life in the balance.

Published online

Journal Article (Review)

Excessive oxygen (O2) can cause tissue injury, scarring, aging, and even death. Our laboratory is studying O2-sensing pulmonary neuroendocrine cells (PNECs) and the PNEC-derived product gastrin-releasing peptide (GRP). Reactive oxygen species (ROS) generated from exposure to hyperoxia, ozone, or ionizing radiation (RT) can induce PNEC degranulation and GRP secretion. PNEC degranulation is also induced by hypoxia, and effects of hypoxia are mediated by free radicals. We have determined that excessive GRP leads to lung injury with acute and chronic inflammation, leading to pulmonary fibrosis (PF), triggered via ROS exposure or by directly treating mice with exogenous GRP. In animal models, GRP-blockade abrogates lung injury, inflammation, and fibrosis. The optimal time frame for GRP-blockade and the key target cell types remain to be determined. The concept of GRP as a mediator of ROS-induced tissue damage represents a paradigm shift about how O2 can cause injury, inflammation, and fibrosis. The host PNEC response in vivo may depend on individual ROS sensing mechanisms and subsequent GRP secretion. Ongoing scientific and clinical investigations promise to further clarify the molecular pathways and clinical relevance of GRP in the pathogenesis of diverse pediatric lung diseases.

Full Text

Duke Authors

Cited Authors

  • Sunday, ME

Published Date

  • 2014

Published In

Volume / Issue

  • 2 /

Start / End Page

  • 72 -

PubMed ID

  • 25101250

Pubmed Central ID

  • 25101250

International Standard Serial Number (ISSN)

  • 2296-2360

Digital Object Identifier (DOI)

  • 10.3389/fped.2014.00072


  • eng

Conference Location

  • Switzerland