Maternal hyperglycemia modifies extracellular matrix signaling pathways in neonatal rat lung.
BACKGROUND
Maternal diabetes is associated with numerous adverse effects in fetal and neonatal organs, including the lungs.


OBJECTIVE
To investigate the effects of intrauterine hyperglycemia on neonatal lung biological signaling, we performed a microarray analysis in the lungs of four 14-day-old rat pups born to a hyperglycemic dam and in four age mate control pup lungs.


METHODS
Total RNA was isolated and cDNA was hybridized to the Illumina Sentrix® RatRef-12 BeadChip. A total of 22,000 genes were analyzed for expression profiles and functional gene clustering. Ten selected genes differentially expressed in microarray were additionally analyzed by the real-time polymerase chain reaction.


RESULTS
Two hundred twenty-seven genes were differentially expressed in neonatal rat lungs exposed to intrauterine hyperglycemia when compared to normoglycemic controls (fold change > 1.2, p < 0.001). Functional clustering analysis revealed increased expression in signaling pathways involved with extracellular matrix regulation. The most significantly downregulated functions were cell proliferation, extracellular region, cell adhesion and reactive oxygen species metabolism.


CONCLUSIONS
We found significant hyperglycemia-induced gene expression alterations in neonatal rat pulmonary tissue which may interfere with lung growth and biological signaling pathways.
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland. anviar @ utu.fi
Anna
A
Koskinen
Asta
A
Laiho
Heikki
H
Lukkarinen
Pekka
P
Kääpä
Hanna
H
Soukka
D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000032:analysis; D002448:Cell Adhesion; D049109:Cell Proliferation; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006943:Hyperglycemia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D007774:Lactation; D008168:Lung / Q000254:growth & development / Q000378:metabolism*; D008431:Maternal-Fetal Exchange / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D046888:Tissue Array Analysis; D015430:Weight Gain
D001786:Blood Glucose; D012333:RNA, Messenger; D017382:Reactive Oxygen Species