Related Experiment Video

Updated: Jan 4, 2026

Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium
08:46

Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium

Published on: September 1, 2015

10.1K

The PI3K/Akt/mTOR pathway in polycystic kidney disease: A complex interaction with polycystins and primary cilium

Jean Piero Margaria1, Carlo Cosimo Campa2, Maria Chiara De Santis1

  • 1Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino 10126, Italy.

Cellular Signalling
|November 13, 2019
PubMed

Insights

Over-activation of the PI3K/Akt/mTOR pathway drives cell hyper-proliferation in polycystic kidney disease (PKD). Targeting mTOR shows promise, but its complex interactions with polycystins and phosphoinositides are key for effective PKD treatments.

Area of Science:

  • Cell biology
  • Molecular medicine
  • Renal pathophysiology

Background:

  • The PI3K/Akt/mTOR pathway is crucial for cell growth and metabolism.
  • Aberrant activation of this network contributes to hyper-proliferation in diseases like cancer and polycystic kidney disease (PKD).
  • In PKD, mTOR signaling promotes cystogenesis by increasing kidney tubule epithelial cell proliferation, size, and metabolism.

Purpose of the Study:

  • To review recent findings on mTOR activation mechanisms in kidney tubule epithelial cells and cyst formation.
  • To discuss the upstream regulation of mTOR by the PI3K/Akt axis in the context of PKD.
  • To explore the interplay between the PI3K/Akt/mTOR network and cyst formation suppression pathways, including polycystins and phosphoinositides.

Main Methods:

  • Literature review of pre-clinical and clinical studies on mTOR inhibition in PKD.
  • Analysis of molecular mechanisms underlying mTOR activation in kidney tubule cells.
  • Dissection of signaling network interactions, including PI3K/Akt/mTOR, polycystins, and phosphoinositides.

Main Results:

  • mTOR cascade significantly contributes to cyst growth in PKD by enhancing cell proliferation, size, and metabolism.
  • Pre-clinical studies show positive results with mTOR inhibition, while clinical trials have been less conclusive.
  • Complex interactions exist between mTORC1 and polycystins, with reciprocal negative regulation observed.
  • Phosphoinositides, modulated by PI3K, play emerging roles in primary cilium signaling, cell polarization, and cyst formation protection.

Conclusions:

  • The PI3K/Akt/mTOR network's role in PKD extends beyond mitogenic signaling, impacting kidney tubule homeostasis and morphogenesis.
  • Understanding these complex interactions is vital for developing more effective therapeutic strategies for PKD.
  • Targeting the PI3K/Akt/mTOR pathway, considering its intricate connections, holds potential for future PKD clinical trials.
Keywords:
CancerPI3KPIK3C2APhosphoinositidesPolycystic kidney diseasePolycystinsPrimary ciliummTOR

More Related Videos

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

821
Spectral Karyotyping to Study Chromosome Abnormalities in Humans and Mice with Polycystic Kidney Disease12:47

Spectral Karyotyping to Study Chromosome Abnormalities in Humans and Mice with Polycystic Kidney Disease

Published on: February 3, 2012

39.1K

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.2K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.6K
Microtubules in Signaling01:22

Microtubules in Signaling

The primary cilium, made up of microtubules, acts as antennae on the cell surfaces for relaying external stimuli into the cells. These fine hair-like structures are present, generally one per cell. These are non-motile cilia in a 9+0 microtubules arrangement, where the central pair of microtubules are absent. The primary cilia arise from the basal body embedded in the cell membrane. Intraflagellar transport (IFT) carries requisite proteins from the cytoplasm to the cilium because the primary...
2.0K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.1K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
11.7K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.5K