PMID- 30057316 OWN - NLM STAT- MEDLINE DCOM- 20190312 LR - 20190312 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 503 IP - 3 DP - 2018 Sep 10 TI - Pioglitazone induces hypoxia-inducible factor 1 activation in human renal proximal tubular epithelial cell line HK-2. PG - 1682-1688 LID - S0006-291X(18)31601-2 [pii] LID - 10.1016/j.bbrc.2018.07.099 [doi] AB - 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 (PPARgamma) 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 PPARgamma agonist, pioglitazone, induces HIF-1 activation or not. Treatment with pioglitazone induced HIF-1alpha mRNA as well as PPARgamma 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 GLUT1 and ABCG2 mRNAs, protein expression of GLUT1 and BCRP was increased by pioglitazone. In addition, GLUT inhibitor phloretin-sensitive D-[(3)H]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 PPARgamma activation by pioglitazone leads to HIF-1 protein expression induction followed by changes in HIF-1 target gene expression and protein product activity. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Urakami-Takebayashi, Yumiko AU - Urakami-Takebayashi Y AD - Department of Pharmaceutics, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan. FAU - Kuroda, Yukimi AU - Kuroda Y AD - Department of Pharmaceutics, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan. FAU - Murata, Tadashi AU - Murata T AD - Department of Pharmaceutics, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan. FAU - Miyazaki, Makoto AU - Miyazaki M AD - Department of Pharmaceutics, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan. FAU - Nagai, Junya AU - Nagai J AD - Department of Pharmaceutics, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan. Electronic address: jnagai@gly.oups.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180727 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Hypoxia-Inducible Factor 1) RN - 0 (RNA, Messenger) RN - X4OV71U42S (Pioglitazone) SB - IM MH - Cells, Cultured MH - Dose-Response Relationship, Drug MH - Epithelial Cells/*drug effects/metabolism MH - Humans MH - Hypoxia-Inducible Factor 1/genetics/*metabolism MH - Pioglitazone/*pharmacology MH - RNA, Messenger/genetics/metabolism MH - Structure-Activity Relationship OTO - NOTNLM OT - Breast cancer resistance protein OT - Facilitative glucose transporter OT - Hypoxia-inducible factor-1 OT - Peroxisome proliferator-activated receptor gamma OT - Pioglitazone OT - Renal proximal tubular cells EDAT- 2018/07/31 06:00 MHDA- 2019/03/13 06:00 CRDT- 2018/07/31 06:00 PHST- 2018/07/18 00:00 [received] PHST- 2018/07/20 00:00 [accepted] PHST- 2018/07/31 06:00 [pubmed] PHST- 2019/03/13 06:00 [medline] PHST- 2018/07/31 06:00 [entrez] AID - S0006-291X(18)31601-2 [pii] AID - 10.1016/j.bbrc.2018.07.099 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2018 Sep 10;503(3):1682-1688. doi: 10.1016/j.bbrc.2018.07.099. Epub 2018 Jul 27.