PPARγ stimulates expression of L-type amino acid and taurine transporters in human placentas: the evidence of PPARγ regulating fetal growth.

Zhaoguang Chen,Ping He,Xin Ni,Xiaoying Ding,Ying Huang,Hang Gu

doi:10.1038/srep12650

Abstract

Placental amino acid transporters and peroxisome proliferator-activated receptors (PPARs) have been implicated to placental development and therefore regulation of fetal growth. We analyzed the correlation between the expression of amino acid transporters and PPARs and investigated whether PPARs control the expression of amino acid transporters in placentas. It was found that protein expression of PPARγ and L-type amino acid transporter 1(LAT1) and 2 (LAT2) was decreased in small-for-gestational-age (SGA) placentas. LAT1, LAT2 and taurine transporter (TAUT) expression correlated to PPARγ level and birth weight. In cultured placental cells, PPARγ agonist stimulated LAT1 and LAT2 and TAUT, which was reversed by PPARγ siRNA. PPARγ up-regulation of LAT1 and TAUT was through specificity protein 1 (Sp-1) while stimulation of LAT2 expression was via induction of gene transcription. Our data suggest that PPARγ, SP-1, LAT1 and LAT2 in placentas are involved in control of fetal growth. PPARγ signaling pathway may be the therapeutic target for intrauterine growth restriction.

Highlights

The exchange of nutrients across the placenta is indispensable for fetal growth over the course of gestation
There was no significant difference in Peroxisome proliferator activated receptors (PPARs) α and PPAR β /δ expression among small-for-gestational age (SGA), appropriate-for-gestational age (AGA) and LGA groups
PPARγ expression correlated to LAT1, LAT2 and taurine transporter (TAUT) level (P < 0.01, supplement Fig. 1), indicating that LAT1, LAT2 and TAUT might be regulated by PPAR γ

Summary

Introduction

The exchange of nutrients across the placenta is indispensable for fetal growth over the course of gestation. Results The expression of LAT1 and LAT2 is significantly decreased in SGA placentas and correlates to PPARγ level and birth weight. Treatment of the cells with increasing concentration of PPARγ agonist rosiglitazone (10−12–10−6M) for 24 h resulted an increase in LAT1, LAT2, TAUT mRNA and protein expression in a dose-dependent manner (Fig. 2A).

Results

Conclusion