We previously reported that fatty acid-bearing albumin but not fatty acid-depleted albumin induces hypoxia-inducible factor-1 (HIF-1) activation in human renal proximal tubular epithelial cell line HK-2. Then, an increase in mRNA expression of peroxisome proliferator-activated receptor gamma (PPAR gamma) was observed on treatment with fatty acid-bearing albumin but not fatty acid-depleted albumin. The aim of this study was to determine whether a PPAR gamma agonist, pioglitazone, induces HIF-1 activation or not. Treatment with pioglitazone induced HIF-1 alpha mRNA as well as PPAR gamma mRNA expression in a concentration dependent manner. In addition, pioglitazone increased HIF-1 target genes such as the mRNAs of glucose transporter 1 (GLUT1) and breast cancer resistance protein (BCRP/ABCG2), in a concentration-dependent manner. Consistent with the increases in GLUTI and ABCG2 mRNA5, protein expression of GLUTI and BCRP was increased by pioglitazone. In addition, GLUT inhibitor phloretin-sensitive D-[H-3] glucose uptake activity and BCRP inhibitor Ko143-sensitive accumulation of Hoecsht33342, a BCRP substrate, were significantly enhanced by treatment with pioglitazone. These findings suggest that PPAR gamma activation by pioglitazone leads to HIF-1 protein expression induction followed by changes in HIF-1 target gene expression and protein product activity. (C) 2018 Elsevier Inc. All rights reserved.