Related Experiment Video

Updated: Nov 10, 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

660

JNK signaling prevents biliary cyst formation through a CASPASE-8-dependent function of RIPK1 during aging

Katrin Müller1, Hanna Honcharova-Biletska2, Christiane Koppe1

  • 1Division of Biliary and Gastrointestinal Oncology, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, 52074 Aachen, Germany.

Proceedings of the National Academy of Sciences of the United States of America
|April 2, 2021
PubMed

Insights

The c-Jun N-terminal kinase (JNK) pathway regulates liver aging. Ablating JNK1 and JNK2 in liver cells causes biliary cysts via RIPK1, linking stress adaptation to cell death.

Area of Science:

  • Hepatology
  • Molecular Biology
  • Aging Research

Background:

  • The c-Jun N-terminal kinase (JNK) pathway is crucial for stress response and implicated in liver diseases.
  • Previous studies primarily investigated JNK function in young animals, leaving its role in liver aging unclear.

Purpose of the Study:

  • To investigate the role of JNK signaling in liver homeostasis during aging.
  • To elucidate the mechanisms underlying age-related liver pathologies associated with JNK deficiency.

Main Methods:

  • Generation of mice with conditional knockout of JNK1 and JNK2 in liver parenchymal cells (JNK1/2LPC-KO).
  • Analysis of liver morphology, cell death pathways, and gene expression in aging JNK1/2LPC-KO mice.
  • Investigation of RIPK1 involvement in cystogenesis.

Main Results:

  • Aging JNK1/2LPC-KO mice spontaneously developed large biliary cysts originating from the biliary compartment.
  • Cyst formation was dependent on receptor-interacting protein kinase 1 (RIPK1).
  • RIPK1 was overexpressed in human polycystic liver disease cyst epithelium.

Conclusions:

  • JNK signaling is essential for maintaining liver homeostasis during aging.
  • A functional link exists between JNK, RIPK1, and age-related biliary cyst development.
  • This study connects stress adaptation pathways with programmed cell death in liver aging.
Keywords:
MK2cholangiocytesliverliver cystsprogrammed cell death

More Related Videos

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis08:55

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis

Published on: August 7, 2018

11.1K
Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells09:15

Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells

Published on: October 20, 2022

2.5K

Related Concept Videos

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...
10.0K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.2K
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...
8.4K
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...
7.1K
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...
6.8K
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...
7.3K