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

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.