FGF23 modulates the effects of erythropoietin on gene expression in renal epithelial cells
| Autor: | Takashi Shigematsu, Kouichi Tatsuta, Mitsuru Yashiro, Shigeo Negi, Ishizawa Yohei, Yuko Iwashita, Masaki Ohya, Takurou Yano, Shuto Yamamoto, Yusuke Tanaka, Sou Kobayashi, Toru Mima, Ryo Matoba, Tomohiro Shoshihara, Yuri Nakashima, Yu Iwashita, Kazuki Kawakami, Ueda Yumi, Tomohiro Sonou, Kouji Okuda |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway bioinformatics analysis PPARγ International Journal of Nephrology and Renovascular Disease 030232 urology & nephrology urologic and male genital diseases 03 medical and health sciences 0302 clinical medicine Mediator STAT1 Downregulation and upregulation FGF23 Gene expression medicine STAT3 Original Research nonprotein-coding gene biology business.industry DNA microarray Cell biology stomatognathic diseases 030104 developmental biology Nephrology Erythropoietin biology.protein Phosphorylation business medicine.drug |
| Zdroj: | International Journal of Nephrology and Renovascular Disease |
| ISSN: | 1178-7058 |
| Popis: | Mitsuru Yashiro,1 Masaki Ohya,1 Toru Mima,1 Yumi Ueda,2 Yuri Nakashima,1 Kazuki Kawakami,1 Yohei Ishizawa,2 Shuto Yamamoto,1 Sou Kobayashi,1 Takurou Yano,1 Yusuke Tanaka,1 Kouji Okuda,1 Tomohiro Sonou,1 Tomohiro Shoshihara,1 Yuko Iwashita,1 Yu Iwashita,1 Kouichi Tatsuta,1 Ryo Matoba,2 Shigeo Negi,1 Takashi Shigematsu1 1Department of Nephrology, Wakayama Medical University, Wakayama, Japan; 2DNA Chip Research Inc., Minato, Japan Background: FGF23 plays an important role in calcium–phosphorus metabolism. Other roles of FGF23 have recently been reported, such as commitment to myocardium enlargement and immunological roles in the spleen. In this study, we aimed to identify the roles of FGF23 in the kidneys other than calcium–phosphorus metabolism. Methods: DNA microarrays and bioinformatics tools were used to analyze gene expression in mIMCD3 mouse renal tubule cells following treatment with FGF23, erythropoietin and/or an inhibitor of ERK. Results: Three protein-coding genes were upregulated and 12 were downregulated in response to FGF23. Following bioinformatics analysis of these genes, PPARγ and STAT3 were identified as candidate transcript factors for mediating their upregulation, and STAT1 as a candidate for mediating their downregulation. Because STAT1 and STAT3 also mediate erythropoietin signaling, we investigated whether FGF23 and erythropoietin might show interactive effects in these cells. Of the 15 genes regulated by FGF23, 11 were upregulated by erythropoietin; 10 of these were downregulated following cotreatment with FGF23. Inhibition of ERK, an intracellular mediator of FGF23, reversed the effects of FGF23. However, FGF23 did not influence STAT1 phosphorylation, suggesting that it impinges on erythropoietin signaling through other mechanisms. Conclusion: Our results suggest cross talk between erythropoietin and FGF23 signaling in the regulation of renal epithelial cells. Keywords: FGF23, STAT1, PPARγ, DNA microarray, bioinformatics analysis, nonprotein-coding gene |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|