Related Experiment Video

Updated: May 29, 2025

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
12:02

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

Published on: June 6, 2017

27.2K

CCN2 functions as a modulator of cell cycle regulation in human dermal fibroblasts

Taihao Quan1, Yuan Shao1, Trupta Purohit1

  • 1Department of Dermatology University of Michigan Medical School Ann Arbor Michigan USA.

Journal of Cell Communication and Signaling
|February 3, 2025
PubMed

Insights

Cellular communication network factor 2 (CCN2) is a novel cell cycle regulator in human dermal fibroblasts (HDFs). It controls fibroblast proliferation by influencing cell cycle progression and is a target of YAP/TAZ signaling.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Fibrosis Research

Background:

  • Cellular communication network factor 2 (CCN2) is primarily known for its role as a profibrotic factor, regulating extracellular matrix (ECM) production in fibrotic disorders.
  • Its function in regulating cell proliferation, particularly in the context of the cell cycle, remains less understood.

Purpose of the Study:

  • To investigate the novel function of CCN2 as a cell cycle regulator in primary human dermal fibroblasts (HDFs).
  • To elucidate the molecular mechanisms underlying CCN2's role in fibroblast proliferation.
  • To explore the relationship between CCN2 and YAP/TAZ signaling in HDFs proliferation.

Main Methods:

  • Small interfering RNA (siRNA)-mediated knockdown of CCN2 in primary HDFs.
  • Rescue experiments using a siRNA-resistant CCN2 expression vector.
  • Cell cycle analysis (e.g., flow cytometry) to assess phase distribution.
  • Western blotting and kinase assays to evaluate protein expression and activity (e.g., cyclins, CDKs).
  • Immunofluorescence microscopy to determine subcellular localization of CCN2.

Main Results:

  • CCN2 knockdown significantly inhibited primary HDF proliferation, which was reversible with CCN2 re-expression.
  • CCN2 depletion led to cell cycle arrest in the G1/G0 phase, preventing entry into S-phase.
  • Knockdown of CCN2 disrupted nuclear translocation of cyclin E and CDK4/cyclin D, and reduced CDK2 activity.
  • CCN2 was found to translocate to the nucleus and co-localize with cyclin D1 during cell cycle stimulation.
  • CCN2 was confirmed as a YAP/TAZ target gene, partially mediating YAP/TAZ-driven proliferation in HDFs.

Conclusions:

  • CCN2 plays a critical role as a cell cycle regulator in primary human dermal fibroblasts.
  • CCN2 influences HDF proliferation by controlling cell cycle progression through modulation of key cell cycle proteins.
  • CCN2 represents a novel mediator of YAP/TAZ-driven proliferation in fibroblasts, expanding its known functions beyond ECM regulation.
Keywords:
CCN2cell cyclefibroblast

More Related Videos

Evaluation of Keratinocyte Proliferation on Two- and Three-dimensional Type I Collagen Substrates08:19

Evaluation of Keratinocyte Proliferation on Two- and Three-dimensional Type I Collagen Substrates

Published on: April 22, 2019

7.0K
Generation and Culturing of Primary Human Keratinocytes from Adult Skin10:42

Generation and Culturing of Primary Human Keratinocytes from Adult Skin

Published on: December 22, 2017

16.3K

Related Concept Videos

Molecular Factors Affecting Cell Division01:27

Molecular Factors Affecting Cell Division

Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
3.0K
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
5.3K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.6K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.4K
The Cell Cycle Control System02:11

The Cell Cycle Control System

The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...
12.0K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.1K