Related Experiment Video

Updated: Jun 28, 2026

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

Sirolimus interacts with pathways essential for podocyte integrity

Emmanuel Letavernier1, Patrick Bruneval, Sophie Vandermeersch

  • 1INSERM, U702 and Université Pierre et Marie Curie-Paris 6, UMRS702, Paris, France. emmanuel.letavernier@tnn.ap-hop-paris.fr

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
|October 18, 2008
PubMed
Abstract

Insights

Sirolimus, an mTOR inhibitor, may harm kidney podocytes by decreasing WT1 expression, potentially leading to glomerular injury and nephrotic syndrome after transplantation. Further research is needed to understand these mechanisms.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Pharmacology

Background:

  • Sirolimus (mTOR inhibitor) is linked to kidney damage, including nephrotic syndrome and glomerular lesions post-transplantation.
  • Podocyte injury and focal segmental glomerulosclerosis are suspected complications of sirolimus therapy, but underlying pathways are unclear.

Purpose of the Study:

  • To investigate the mechanisms by which sirolimus affects human podocytes.
  • To elucidate the role of sirolimus in podocyte injury and potential glomerular damage.

Main Methods:

  • Primary human podocyte cultures were treated with therapeutic concentrations of sirolimus.
  • Assessed cell viability, cytoskeleton, VEGF synthesis, Akt phosphorylation, and WT1 expression.

Main Results:

  • Sirolimus did not affect podocyte viability but altered cell phenotype and cytoskeleton.
  • Decreased vascular endothelial growth factor (VEGF) synthesis and Akt phosphorylation were observed.
  • Sirolimus dose-dependently reduced WT1 gene and protein expression, a key factor for podocyte integrity.

Conclusions:

  • Sirolimus may impair pathways crucial for podocyte integrity.
  • These effects suggest sirolimus could predispose patients to glomerular injury.
  • Understanding these mechanisms is vital for managing sirolimus-related nephrotoxicity.

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 rapamycin-insensitive companion...
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...
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...
Drug Elimination by Renal Route: Tubular Secretion01:15

Drug Elimination by Renal Route: Tubular Secretion

Once the process of glomerular filtration is completed, blood carrying unfiltered drug molecules traverses through efferent arterioles and makes its way into the peritubular capillaries in the proximal tubule. A variety of carriers play a pivotal role in actively secreting drugs from these peritubular capillaries into the tubular fluid. The organic anion transporter transfers acidic drugs, against an electrochemical gradient, from the peritubular capillaries into the renal tubule cells and...
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...
Diabetic Nephropathy01:28

Diabetic Nephropathy

Definition Diabetic nephropathy is a chronic kidney complication that results from prolonged hyperglycemia.Prevalence It is the most common cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide, affecting up to half of individuals with diabetes.Pathophysiology • Sustained hyperglycemia triggers multiple hemodynamic and metabolic changes in the kidney. • Early in the disease, increased renal blood flow and glomerular hyperfiltration occur due to afferent arteriolar...