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

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 P...

Full description

Saved in:
Bibliographic Details
Published in:FEBS letters 2019-08, Vol.593 (16), p.2261-2272
Main Authors: Maity, Soumya, Das, Falguni, Ghosh‐Choudhury, Nandini, Kasinath, Balakuntalam S., Ghosh Choudhury, Goutam
Format: Article
Language:English
Subjects:
diabetic nephropathy
fibrosis
microRNA
renal cell hypertrophy
signal transduction
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0014-5793
1873-3468
DOI:10.1002/1873-3468.13505