High glucose increases miR-214 to power a feedback loop involving PTEN and the Akt/mTORC1 signaling axis

Soumya Maity, Falguni Das, Nandini Ghosh-Choudhury, Balakuntalam S. Kasinath, Goutam Ghosh Choudhury

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

The mechanism of PTEN repression by high glucose in diabetic nephropathy is not known. Using proximal tubular cells, we show that inhibition of PI3 kinase/Akt and their inactive enzymes prevents high glucose-induced PTEN downregulation. Similarly, rapamycin (Rapa) and shRaptor block suppression of PTEN by high glucose. In contrast, the constitutive activation of Akt and mechanistic target of rapamycin (mTOR)C1 decrease the expression of PTEN, similarly to high glucose. Remarkably, PI3 kinase/Akt/mTORC1 inhibition significantly attenuates high glucose-stimulated increase in miR-214, which targets PTEN, while constitutively active Akt/mTORC1 increases miR-214. Furthermore, anti-miR-214 and mTORC1 inhibition block high glucose-induced hypertrophy and fibronectin expression. These results reveal the first evidence for the presence of a high glucose-forced positive feedback conduit between the three-layered kinase cascade and miR-214/ PTEN in tubular cell injury.

Original languageEnglish (US)
Pages (from-to)2261-2272
Number of pages12
JournalFEBS Letters
Volume593
Issue number16
DOIs
StatePublished - 2019

Keywords

  • diabetic nephropathy
  • fibrosis
  • microRNA
  • renal cell hypertrophy
  • signal transduction

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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