Diagenode

The TGF-β profibrotic cascade targets ecto-5'-nucleotidase gene in proximal tubule epithelial cells and is a traceable marker of progressive diabetic kidney disease.


Cappelli C, Tellez A, Jara C, Alarcón S, Torres A, Mendoza P, Podestá L, Flores C, Quezada C, Oyarzún C, Martín RS

Progressive diabetic nephropathy (DN) and loss of renal function correlate with kidney fibrosis. Crosstalk between TGF-β and adenosinergic signaling contributes to the phenotypic transition of cells and to renal fibrosis in DN models. We evaluated the role of TGF-β on NT5E gene expression coding for the ecto-5`-nucleotidase CD73, the limiting enzyme in extracellular adenosine production. We showed that high d-glucose may predispose HK-2 cells towards active transcription of the proximal promoter region of the NT5E gene while additional TGF-β results in full activation. The epigenetic landscape of the NT5E gene promoter was modified by concurrent TGF-β with occupancy by the p300 co-activator and the phosphorylated forms of the Smad2/3 complex and RNA Pol II. Transcriptional induction at NT5E in response to TGF-β was earlier compared to the classic responsiveness genes PAI-1 and Fn1. CD73 levels and AMPase activity were concomitantly increased by TGF-β in HK-2 cells. Interestingly, we found increased CD73 content in urinary extracellular vesicles only in diabetic patients with renal repercussions. Further, CD73-mediated AMPase activity was increased in the urinary sediment of DN patients. We conclude that the NT5E gene is a target of the profibrotic TGF-β cascade and is a traceable marker of progressive DN.

Tags
Antibody

Share this article

Published
April, 2020

Source

Products used in this publication

  • cut and tag antibody icon
    C15410195
    H3K27me3 polyclonal antibody
  • cut and tag antibody icon
    C15410003-50
    H3K4me3 polyclonal antibody
  • cut and tag antibody icon
    C15410200
    H3K9/14ac polyclonal antibody
  • Antibody ChIP icon
    C15310135
    H3pan polyclonal antibody
  • ChIP-seq Grade
    C15200211
    p300 monoclonal antibody
  • Mouse IgG
    C15410273
    SMAD2 polyclonal antibody

イベント

  • Long-Read Sequencing Meeting 2024
    Uppsala, Sweden
    Oct 21-Oct 23, 2024
  • NextGen Omics 2024
    London, UK
    Oct 23-Oct 25, 2024
  • FEBS 2024
    Budapest, Hungary
    Oct 28-Oct 31, 2024
  • 5th Danube Conference on Epigenetics
    Budapest, Hungary
    Oct 28-Oct 31, 2024
 すべてのイベントを見る

 


       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy