Related Experiment Video

Updated: Jun 2, 2025

A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth
06:35

A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth

Published on: December 22, 2020

4.4K

Chloride intracellular channel CLIC3 mediates fibroblast cellular senescence by interacting with ERK7

Changjiao Luan1,2, Yue Gao1,3, Jun Zhao2

  • 1Laboratory of Intensive Care, Laboratory for Prevention and Translation of Geriatric Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou, China.

Communications Biology
|January 14, 2025
PubMed

Insights

Chloride intracellular channel 3 (CLIC3) drives cellular senescence (CS) and aging by interacting with ERK7. Reducing CLIC3 alleviates aging markers and senescence-associated secretory phenotype (SASP).

Area of Science:

  • Cellular and Molecular Biology
  • Aging Research
  • Ion Channel Physiology

Background:

  • Cellular senescence (CS) is a key factor in aging and age-related diseases.
  • Ion channels are increasingly recognized as crucial mediators of CS.
  • The specific roles of chloride intracellular channels (CLICs) in CS are not well understood.

Purpose of the Study:

  • To investigate the role and regulatory mechanisms of CLICs in cellular senescence.
  • To identify specific CLIC members involved in CS.
  • To elucidate the molecular pathways through which CLICs modulate CS.

Main Methods:

  • RNA sequencing of bleomycin-induced senescent mouse lung tissue.
  • Knockdown of Chloride Intracellular Channel 3 (CLIC3).
  • Assessment of intracellular chloride ion levels, mitochondrial function, nuclear morphology, DNA damage, and SASP markers.

Main Results:

  • Clic3 was identified as the most upregulated CLIC member in senescent lung tissue.
  • CLIC3 knockdown reduced intracellular chloride loss, mitochondrial dysfunction, nuclear enlargement, DNA damage, and SASP.
  • CLIC3 was found to translocate to the membrane and interact with extracellular signal-regulated kinase 7 (ERK7), repressing its activity.

Conclusions:

  • Chloride intracellular channel 3 (CLIC3) plays a significant role in modulating cellular senescence.
  • CLIC3 regulates CS by interacting with and inhibiting ERK7 activity.
  • This study provides novel insights into the function of chloride channels in aging and senescence.

More Related Videos

Techniques to Induce and Quantify Cellular Senescence06:51

Techniques to Induce and Quantify Cellular Senescence

Published on: May 1, 2017

33.1K
Induction and Analysis of Epithelial to Mesenchymal Transition10:37

Induction and Analysis of Epithelial to Mesenchymal Transition

Published on: August 27, 2013

35.7K

Related Concept Videos

Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
3.6K
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
2.5K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
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...
7.2K
Cell Motility through Blebbing01:16

Cell Motility through Blebbing

Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
Blebbing Through the Matrix
In multicellular...
1.9K
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.2K