Related Experiment Video

Updated: Aug 10, 2026

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
07:49

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling

Published on: August 3, 2018

Involvement of calcineurin in transforming growth factor-beta-mediated regulation of extracellular matrix

Jennifer L Gooch1, Yves Gorin, Bin-Xian Zhang

  • 1Department of Medicine, Division of Nephrology, University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA. Gooch@uthscsa.edu

The Journal of Biological Chemistry
|January 27, 2004
PubMed

Insights

Transforming growth factor-beta (TGF-beta) activates calcineurin phosphatase activity, crucial for extracellular matrix (ECM) protein accumulation. This pathway involves reactive oxygen species (ROS) and calcium influx, highlighting a novel TGF-beta signaling mechanism.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Biochemistry

Background:

  • Calcineurin is a calcium-dependent phosphatase involved in cellular signaling.
  • Transforming growth factor-beta (TGF-beta) regulates various cellular processes.
  • The precise role of calcineurin in TGF-beta-mediated effects requires elucidation.

Purpose of the Study:

  • To investigate the role of calcineurin in TGF-beta-induced cellular effects.
  • To identify the signaling pathway responsible for calcineurin activation by TGF-beta.
  • To explore the relationship between TGF-beta, calcineurin, and extracellular matrix (ECM) production.

Main Methods:

  • Investigated calcineurin activation by TGF-beta using time- and dose-dependent assays.
  • Assessed NFATc1 dephosphorylation and nuclear translocation as indicators of calcineurin activity.
  • Utilized calcineurin inhibition and overexpression to determine its necessity and sufficiency in TGF-beta signaling.
  • Measured intracellular calcium levels and employed calcium chelation to study calcium's role.
  • Analyzed the involvement of reactive oxygen species (ROS) in calcineurin activation.

Main Results:

  • TGF-beta activates calcineurin in a time- and dose-dependent manner.
  • Calcineurin activation leads to NFATc1 dephosphorylation and nuclear translocation.
  • Calcineurin is essential for TGF-beta-mediated ECM protein accumulation but not cell hypertrophy.
  • TGF-beta induces a sustained increase in intracellular calcium, required for calcineurin activation.
  • Calcium influx is dependent on ROS generation (superoxide anion and hydrogen peroxide).
  • Inhibition of ROS generation blocks TGF-beta-induced calcineurin activity and ECM accumulation.

Conclusions:

  • A novel pathway for TGF-beta-mediated ECM regulation is described.
  • This pathway involves ROS generation, calcium influx, and subsequent calcineurin activation.
  • Calcineurin plays a critical role in TGF-beta-induced extracellular matrix production.

More Related Videos

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay11:38

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay

Published on: September 14, 2021

Related Concept Videos

Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
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...
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Extracellular Matrix01:29

The Extracellular Matrix

Overview
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
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...
Cell-matrix's Response to Mechanical Forces01:13

Cell-matrix's Response to Mechanical Forces

In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue. 
Anchoring junctions mechanically attach a cell to the...