Peroxisome proliferator-activated receptor gamma agonists enhance lung maturation in a neonatal rat model.
The nuclear transcription factor peroxisome proliferator-activated receptor (PPAR) gamma plays a central role in normal lung development. However, the effects of modulating PPARgamma expression by exogenously administered PPARgamma agonists on lung development and basic blood biochemical and metabolic profiles in a developing animal are not known. To determine these effects, newborn Sprague-Dawley rat pups were administered either diluent or rosiglitazone (RGZ), a potent PPARgamma agonist, for either 1 or 7 d. Then the pups were killed and the lungs were examined for specific markers of alveolar epithelial, mesenchymal, and vascular maturation, and lung morphometry. The effect of RGZ on a limited number of blood biochemical and metabolic parameters was also determined. Overall, systemically administered RGZ significantly enhanced lung maturation without affecting serum electrolytes, blood glucose, blood gases, plasma cholesterol, triglycerides, and serum cardiac troponin levels. The lung maturation effect of PPARgamma agonists was also confirmed by another PPARgamma agonist, the naturally occurring PPARgamma ligand prostaglandin J2. We conclude that systemically administered RGZ significantly enhances lung maturation without significantly affecting the acute blood biochemical and metabolic profiles, providing rationale for further studying PPARgamma agonists for enhancing lung maturation, and for promoting lung injury/repair in neonates.
Wang
Ying
Y
Department of Pediatrics, David Geffen School of Medicine at University of California, Los Angeles, Torrance, California 90502, USA.
Santos
Jamie
J
Sakurai
Reiko
R
Shin
Eugene
E
Cerny
Laura
L
Torday
John S
JS
Rehan
Virender K
VK
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001784:Blood Gas Analysis; D002454:Cell Differentiation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008648:Mesoderm / Q000187:drug effects / Q000378:metabolism; D023421:Models, Animal; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D000070780:Perilipin-2; D015230:Prostaglandin D2 / Q000008:administration & dosage / Q000031:analogs & derivatives; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019141:Respiratory System Agents / Q000008:administration & dosage*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage*; D013997:Time Factors
D015415:Biomarkers; D008565:Membrane Proteins; D047495:PPAR gamma; D000070780:Perilipin-2; D019141:Respiratory System Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C037112:9-deoxy-delta-9-prostaglandin D2; D015230:Prostaglandin D2