| Autor: |
Padela, Sanna, Cabacungan, Judy, Shek, Samuel, Belcastro, Rosetta, Yi, Man, Jankov, Robert P, Tanswell, A Keith |
| Zdroj: |
American Journal of Respiratory & Critical Care Medicine; 2005, Vol. 172 Issue 7, p907-914, 8p |
| Abstrakt: |
Rationale: Our core hypothesis is that growth factors that have dysregulated expression during experimental neonatal lung injury are likely to be involved in normal postnatal lung growth and alveologenesis.Objectives: To determine if hepatocyte growth factor (HGF) is upregulated in neonatal lung injury and is essential for postnatal alveologenesis.Methods: A neonatal lung injury, in which there were patchy areas of interstitial thickening with a relative increase in the proportion of epithelial cells, was induced in newborn rats by exposing them to 60% oxygen for 14 days. Air-exposed pups had binding of endogenous HGF to its natural receptor, c-Met, inhibited by the intraperitoneal injection of either neutralizing antibody to HGF, or a truncated soluble c-Met receptor.Measurements and Main Results: The 60% oxygen-mediated lung injury was associated with increased lung mRNAs for hepatocyte growth factor and c-Met, relative to air-exposed control lungs, at Day 7 after birth. After exposure to 60% oxygen, immunoreactive HGF was increased at Days 4 and 7, and immunoreactive c-Met was increased at Day 14. In air-exposed pups, intraperitoneal injections of neutralizing antibody to HGF inhibited DNA synthesis in alveoli-forming secondary crests, and reduced the number of alveoli in 6-day-old pups. Intraperitoneal injections of a truncated soluble c-Met receptor inhibited DNA synthesis in secondary crests in 4-day-old air-exposed rat pups.Conclusions: HGF and its c-Met receptor are required for normal postnatal alveolar formation from secondary crests, and are upregulated during 60% oxygen-induced neonatal lung injury. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
