Related Experiment Video

Updated: Aug 25, 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

Inhibition of JNK by HGF/SF prevents apoptosis induced by TNF-alpha

Sylvie Reveneau1, Réjane Paumelle, Julien Deheuninck

  • 1Ecole Pratique des Hautes Etudes, Institut National de la Santé et de la Recherche Médicale U517, BP 87900, 21079 Dijon, France. Sylvie.Reveneau@u-bourgogne.fr

Annals of the New York Academy of Sciences
|March 23, 2004
PubMed

Insights

Hepatocyte growth factor/scatter factor (HGF/SF) prevents cell death by inhibiting JNK signaling in epithelial cells. This protection against tumor necrosis factor-alpha (TNF-alpha) involves PI3K and MEK1 pathways.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Tumor necrosis factor-alpha (TNF-alpha) is a key inducer of apoptosis and JNK pathway activation in epithelial cells.
  • Hepatocyte growth factor/scatter factor (HGF/SF) is known to have protective effects on cells, but the underlying mechanisms are not fully elucidated.
  • Understanding the interplay between HGF/SF, JNK signaling, and apoptosis is crucial for cellular protection strategies.

Purpose of the Study:

  • To investigate if HGF/SF-mediated repression of c-Jun N-terminal kinase (JNK) signaling is linked to its cytoprotective effects against TNF-alpha-induced apoptosis.
  • To identify the specific signaling pathways involved in HGF/SF's protective mechanism against TNF-alpha in Madin-Darby canine kidney (MDCK) epithelial cells.

Main Methods:

  • MDCK epithelial cells were treated with TNF-alpha to induce apoptosis and JNK activation.
  • The effects of HGF/SF on TNF-alpha-induced cell death and JNK activity were assessed.
  • Signaling pathways, including PI3K (phosphatidylinositol 3-kinase) and MEK1 (MAPK/ERK kinase 1), were analyzed to determine their role in HGF/SF's protective effects.

Main Results:

  • HGF/SF significantly repressed TNF-alpha-induced JNK activation in MDCK cells.
  • HGF/SF demonstrated a protective effect against TNF-alpha-induced cell death.
  • The protective action of HGF/SF was found to be mediated through the activation of both the PI3K and MEK1 signaling pathways.

Conclusions:

  • Repression of JNK signaling is a key mechanism by which HGF/SF protects epithelial cells from TNF-alpha-induced apoptosis.
  • Activation of PI3K and MEK1 pathways are critical components of the HGF/SF-mediated cytoprotective signaling cascade.
  • These findings elucidate a novel molecular mechanism for HGF/SF in cellular defense against apoptotic stimuli.

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
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...
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...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.