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Updated: Apr 4, 2026

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
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Halting renal fibrosis: an unexpected role for mTORC2 signaling

Florian Grahammer1

  • 1Renal Division, University Medical Center Freiburg, Freiburg, Germany.

Kidney International
|September 1, 2015
PubMed

Insights

Researchers found that mTORC2 mediates transforming growth factor-β (TGF-β) signaling, a key driver of kidney fibrosis. This discovery highlights mTORC2 as a potential therapeutic target for chronic kidney disease.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cell Signaling

Background:

  • Slowly progressive renal fibrosis is a common characteristic of chronic kidney disease (CKD).
  • Transforming growth factor-beta (TGF-β) is recognized as the primary cytokine driving kidney fibrosis.
  • Existing knowledge points to several profibrotic kinases downstream of TGF-β signaling.

Purpose of the Study:

  • To investigate the role of mTORC2 in mediating TGF-β signaling in renal fibrosis.
  • To identify upstream mediators of TGF-β-induced profibrotic pathways.

Main Methods:

  • Utilized a mouse genetic approach to study the in vivo role of mTORC2 in renal fibrosis.
  • Investigated the signaling pathways downstream of TGF-β, focusing on mTORC2 and its associated kinases.

Main Results:

  • Identified mTORC2 as a crucial mediator in the TGF-β signaling pathway.
  • Demonstrated that mTORC2 acts upstream of previously identified profibrotic kinases including AKT, SGK1, and PKC-α.
  • Mouse genetic studies provided convincing evidence for mTORC2's role.

Conclusions:

  • mTORC2 is a significant upstream mediator of TGF-β-induced renal fibrosis.
  • mTORC2 presents a potential novel drug target for treating chronic kidney disease.
  • Translating these findings from preclinical models to clinical application may face challenges.

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