Clinical and Experimental Nephrology

, Volume 20, Issue 1, pp 30–38 | Cite as

High glucose promotes TGF-β1 production by inducing FOS expression in human peritoneal mesothelial cells

  • Keiko Kokoroishi
  • Ayumu Nakashima
  • Shigehiro Doi
  • Toshinori Ueno
  • Toshiki Doi
  • Yukio Yokoyama
  • Kiyomasa Honda
  • Masami Kanawa
  • Yukio Kato
  • Nobuoki Kohno
  • Takao Masaki
Original Article

Abstract

Background

High glucose (HG) induces production of transforming growth factor-beta1 (TGF-β1), but the mechanism remains elusive. The aim of this study was to determine the gene(s) involved in HG-induced TGF-β1 production in human peritoneal mesothelial cells (HPMCs).

Methods

Microarray analysis was performed following a 3-h preincubation of HPMCs in 4 or 0.1 % glucose medium. Transcriptional genes were selected using Gene Ontology analysis for biological processes, including regulation of transcription and DNA-dependent. The effects of small interfering RNA (siRNA) treatments on the up-regulation of TGF-β1 mRNA were assessed by quantitative real-time polymerase chain reaction (qPCR). Finally, enzyme-linked immunosorbent assay (ELISA) was performed to determine which gene(s) contribute to the production of TGF-β1 protein in the medium.

Results

Microarray analysis revealed that the expression of 51 genes increased by more than 3-fold. Gene ontology analysis identified 13 genes for further study. qPCR confirmed mRNA amplification for 9 of the 13 genes. Furthermore, HG-induced up-regulation of TGF-β1 mRNA was attenuated by the siRNA of 4 genes: MDS1 and EVI1 complex locus (MECOM), FBJ murine osteosarcoma viral oncogene homolog B (FOSB), FBJ murine osteosarcoma viral oncogene homolog (FOS) and activating transcription factor 3 (ATF3). ELISA showed that siRNA treatment of FOS, but not MECOM, FOSB or ATF3, suppressed the increase of TGF-β1 protein in the medium.

Conclusions

FOS is a downstream effector of HG stimulation in HPMCs that contributes to TGF-β1 production, suggesting that blocking FOS expression may be a therapeutic target for peritoneal fibrosis.

Keywords

FOS High glucose Human peritoneal mesothelial cells Microarray TGF-β1 

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Copyright information

© Japanese Society of Nephrology 2015

Authors and Affiliations

  • Keiko Kokoroishi
    • 1
  • Ayumu Nakashima
    • 1
    • 2
  • Shigehiro Doi
    • 1
    • 6
  • Toshinori Ueno
    • 1
  • Toshiki Doi
    • 1
  • Yukio Yokoyama
    • 1
  • Kiyomasa Honda
    • 3
  • Masami Kanawa
    • 4
  • Yukio Kato
    • 3
  • Nobuoki Kohno
    • 5
  • Takao Masaki
    • 1
  1. 1.Department of NephrologyHiroshima University HospitalHiroshimaJapan
  2. 2.Department of Regeneration and Medicine, Medical Center for Translational and Clinical ResearchHiroshima University HospitalHiroshimaJapan
  3. 3.Department of Dental and Medical Biochemistry, Graduate School of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
  4. 4.Natural Science Center for Basic Research and DevelopmentHiroshima UniversityHiroshimaJapan
  5. 5.Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
  6. 6.Department of Blood PurificationHiroshima University HospitalHiroshimaJapan

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