Related Experiment Video

Updated: Oct 15, 2025

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
07:15

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

578

Rapamycin attenuates PLA2R activation-mediated podocyte apoptosis via the PI3K/AKT/mTOR pathway

Terry Ting-Yu Chiou1, You-Ying Chau2, Jin-Bor Chen3

  • 1Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|October 26, 2021
PubMed

Insights

Group IB secretory phospholipase A2 (sPLA2IB) triggers podocyte apoptosis via the PI3K/AKT/mTOR pathway in membranous nephropathy (MN). Rapamycin inhibits this pathway, offering potential therapeutic benefits for MN.

Area of Science:

  • Nephrology
  • Cell Biology
  • Molecular Medicine

Background:

  • Membranous nephropathy (MN) is a leading cause of nephrotic syndrome in adults, often linked to antibodies against phospholipase A2 receptor (PLA2R).
  • The precise signaling pathways involved in PLA2R-mediated podocyte injury and potential therapeutic targets remain incompletely understood.
  • The mammalian target of rapamycin (mTOR) pathway's role in podocyte function and its interplay with PLA2R signaling in MN require further investigation.

Purpose of the Study:

  • To elucidate the crosstalk between phospholipase A2 receptor (PLA2R) activation and mammalian target of rapamycin (mTOR) signaling in human podocytes.
  • To investigate the role of Group IB secretory phospholipase A2 (sPLA2IB) in podocyte apoptosis and its association with the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mTOR pathway.
  • To evaluate the potential of rapamycin and LY294002 in mitigating sPLA2IB-induced podocyte apoptosis.

Main Methods:

  • Utilized a human podocyte cell line exposed to Group IB secretory phospholipase A2 (sPLA2IB).
  • Assessed podocyte apoptosis and the activation status of the PI3K/AKT/mTOR pathway.
  • Investigated the effects of pharmacological inhibitors, including rapamycin and LY294002, on sPLA2IB-induced cellular changes.
  • Analyzed the expression of key proteins involved in both extrinsic and intrinsic apoptotic cascades.

Main Results:

  • sPLA2IB induced podocyte apoptosis in a concentration- and time-dependent manner.
  • sPLA2IB-induced apoptosis was mediated by the upregulation of the PI3K/AKT/mTOR pathway.
  • Inhibition of the PI3K/AKT/mTOR pathway by rapamycin or LY294002 significantly reduced sPLA2IB-induced podocyte apoptosis.
  • Aberrant PI3K/AKT/mTOR activation was found to trigger both extrinsic (caspase-8, caspase-3) and intrinsic (BAX, BCL-2, cytochrome c, caspase-9, caspase-3) apoptotic pathways.

Conclusions:

  • PLA2R activation by sPLA2IB promotes podocyte apoptosis through the PI3K/AKT/mTOR signaling cascade.
  • Inhibiting the PI3K/AKT/mTOR pathway offers a protective effect against podocyte apoptosis in the context of PLA2R activation.
  • Rapamycin demonstrates therapeutic potential for membranous nephropathy by protecting podocytes from apoptosis, supporting its repurposing for MN treatment.
Keywords:
Mammalian target of rapamycinMembranous nephropathyPhospholipase A2 receptorPodocyte

More Related Videos

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes15:43

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Published on: January 7, 2013

18.3K
Author Spotlight: Developing Tools to Tune the Activity of Tyrosine Phosphatases06:56

Author Spotlight: Developing Tools to Tune the Activity of Tyrosine Phosphatases

Published on: September 6, 2024

495

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...
4.2K
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...
3.9K
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...
9.6K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
6.5K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
7.1K