Abnormal platelet-derived growth factor signaling accounting for lung hypoplasia in experimental congenital diaphragmatic hernia

作者：Dingemann Jens; Doi Takashi; Ruttenstock Elke; Puri Prem^*

来源：Journal of Pediatric Surgery, 2010, 45(10): 1989-1994.

DOI：10.1016/j.jpedsurg.2010.06.014

• Congenital diaphragmatic Hernia
• Nitrofen
• Lung development
• PDGF
• Oxidation

Purpose: The pathogenesis of pulmonary hypoplasia in congenital diaphragmatic hernia (CDH) is not fully understood. Platelet-derived growth factor A (PDGFA) and platelet-derived growth factor receptor alpha (PDGFR alpha) play a crucial role in lung development. It has been reported that PDGF induces H(2)O(2)-production and that oxidative stress may be an important mechanism for the impaired lung development in the nitrofen rat model. We hypothesized that pulmonary expression of PDGFA and PDGFR alpha is altered in the nitrofen induced CDH model.
Materials and Methods: Pregnant rats received 100 mg nitrofen or vehicle on gestational day 9 (D9) and were sacrificed on D15, D18 or D21. RNA was extracted from fetal left lungs and mRNA levels of PDGFA and PDGFR alpha were determined using real-time polymerase chain reaction. Immunohistochemistry for protein expression of PDGFA and PDGFR alpha was performed. Pulmonary H(2)O(2) was measured colorimetrically.
Results: mRNA levels of PDGFR alpha at D15 (4.50 +/- 0.87) and PDGFA at D18 (2.90 +/- 1.38) were increased in the nitrofen group (P < .05). Immunohistochemistry revealed increased pulmonary expression of PDGFR alpha and PDGFA. H(2)O(2) content was significantly higher in the nitrofen group.
Conclusions: Increased expression of PDGFA and PDGFR alpha suggests that pulmonary hypoplasia in the nitrofen CDH model may be owing to PDGF-induced oxidative stress during lung development.

• 出版日期2010-10