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 language | English (US) |
|---|---|
| Journal | FEBS Letters |
| DOIs | |
| State | Published - Jan 1 2019 |
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Keywords
- diabetic nephropathy
- fibrosis
- microRNA
- renal cell hypertrophy
- signal transduction
ASJC Scopus subject areas
- Biophysics
- Structural Biology
- Biochemistry
- Molecular Biology
- Genetics
- Cell Biology
Cite this
High glucose increases miR-214 to power a feedback loop involving PTEN and the Akt/mTORC1 signaling axis. / Maity, Soumya; Das, Falguni; Ghosh-choudhury, Nandini; Kasinath, Balakuntalam S; Ghosh-choudhury, Goutam.
In: FEBS Letters, 01.01.2019.Research output: Contribution to journal › Letter
}
TY - JOUR
T1 - High glucose increases miR-214 to power a feedback loop involving PTEN and the Akt/mTORC1 signaling axis
AU - Maity, Soumya
AU - Das, Falguni
AU - Ghosh-choudhury, Nandini
AU - Kasinath, Balakuntalam S
AU - Ghosh-choudhury, Goutam
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
KW - diabetic nephropathy
KW - fibrosis
KW - microRNA
KW - renal cell hypertrophy
KW - signal transduction
UR - http://www.scopus.com/inward/record.url?scp=85068503840&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068503840&partnerID=8YFLogxK
U2 - 10.1002/1873-3468.13505
DO - 10.1002/1873-3468.13505
M3 - Letter
C2 - 31240704
AN - SCOPUS:85068503840
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
ER -