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Human peroxisome proliferator-activated receptor mRNA and protein expression during development
Citation:
WATKINS, A., C. R. WOOD, K. DAS, AND B. D. ABBOTT. Human peroxisome proliferator-activated receptor mRNA and protein expression during development. Presented at Society of Toxicology 49th Annual meeting, Salt Lake City, UT, March 07 - 11, 2010.
Impact/Purpose:
This study profiles human PPAR protein and mRNA expression during development.
Description:
The peroxisome proliferator-activated receptors (PPAR) are nuclear hormone receptors that regulate lipid and glucose homeostasis and are important in reproduction and development. PPARs are targets ofpharmaceuticals and are also activated by environmental contaminants, including perfluorinated alkyl acids. Animal studies have characterized the expression ofPPAR a, r3, and y in mouse and rat, but little is known about PPAR expression during human development. In this study, human fetal adrenal, heart, intestine, kidney, liver, lung, spleen, stomach, and thymus, gestation day 54-120, were obtained from the Birth Defects Research Laboratory at the University of Washington, Seattle. Quantitative PCR was used to evaluate mRNA and Western blot for protein expression ofPPAR a, r3, and y. No significant changes in expression with age were observed for PPARa or PPARy mRJ"l"A in any tissue, but significant decreases in PPARr3wereseen inheartandintestinewithage. The abundance offetal PPAR mRNA was compared to adult human samples (First Choice Human Total RNA, Ambion, Inc.). In liver and intestine, fetal and adult PPAR expression was the same, while in stomach and heart all PPARs had lower expression in fetus. In the kidney and spleen, PPARa and PPARr3 were lower and in lung PPARy was lower in the embryo than in adult. Relative expression ofPPARa, r3, and y varied by tissue. Western blots showed no changes in protein with age for any PPAR isoform in the heart, spleen, stomach or thymus. Decreasing protein with age occurred for PPARa in kidney and lung and PPARy in kidney. However, PPARa increased in intestine and PPARr3increased in liver and intestine. This study profiles human PPAR protein and mRNA expression during development. In general, all PPAR subtypes were detected in all organs and expression appeared stable. Also, with some exceptions, mRNA levels were similar to adult or lower infetus. This studyprovides newinformationregarding humanfetal expression ofPPAR and will be important in evaluating the potential for developing human to respond to PPAR agonists. .