Related Experiment Video

Updated: Aug 10, 2026

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
08:43

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation

Published on: May 31, 2016

Calcineurin-mediated pathway involved in the differentiated phenotype of smooth muscle cells

Yasuyuki Ohkawa1, Ken'ichiro Hayashi, Kenji Sobue

  • 1Department of Neuroscience, Osaka University Graduate School of Medicine (D13), 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.

Biochemical and Biophysical Research Communications
|January 22, 2003
PubMed

Insights

The calcineurin pathway is crucial for maintaining smooth muscle cell (SMC) differentiation. Inhibiting calcineurin causes SMCs to lose their specialized characteristics, highlighting its role in cell phenotype.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Physiology

Background:

  • The calcineurin pathway influences skeletal and cardiac hypertrophy and vascular development.
  • The role of calcineurin in smooth muscle cell (SMC) phenotype is not well understood.
  • Differentiated SMC phenotype is maintained by insulin-like growth factor (IGF-I) activating the phosphatidylinositol 3-kinase (PI3-K)/protein kinase B (PKB(Akt)) pathway.

Purpose of the Study:

  • To investigate the role of the calcineurin-mediated pathway in maintaining the differentiated phenotype of SMCs.
  • To determine the relationship between the calcineurin pathway and SMC differentiation.
  • To elucidate the molecular mechanisms linking calcineurin signaling to SMC phenotype.

Main Methods:

  • Used cultured visceral SMCs as a model for differentiated SMCs.
  • Administered calcineurin inhibitors (cyclosporin A, FK506) and expressed a calcineurin inhibitor (CAIN).
  • Blocked the PI3-K/PKB(Akt) pathway and expressed constitutively active calcineurin Aalpha to assess promoter activities of SMC markers (caldesmon, alpha1 integrin).

Main Results:

  • Calcineurin inhibitors and CAIN expression induced SMC dedifferentiation.
  • Blocking the PI3-K/PKB(Akt) pathway suppressed promoter activities of SMC markers.
  • Forced expression of active calcineurin Aalpha rescued the suppression of SMC marker promoter activities.

Conclusions:

  • The calcineurin-mediated pathway is essential for maintaining the differentiated phenotype of SMCs.
  • The calcineurin pathway functions downstream of the PI3-K/PKB(Akt) pathway in regulating SMC differentiation.
  • Targeting the calcineurin pathway could offer therapeutic strategies for SMC-related conditions.

More Related Videos

Quantitative Analysis of Cellular Composition in Advanced Atherosclerotic Lesions of Smooth Muscle Cell Lineage-Tracing Mice09:06

Quantitative Analysis of Cellular Composition in Advanced Atherosclerotic Lesions of Smooth Muscle Cell Lineage-Tracing Mice

Published on: February 20, 2019

Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro08:28

Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro

Published on: February 15, 2022

Related Concept Videos

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 until 1985...
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,...
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...
Smooth Muscle Contraction01:25

Smooth Muscle Contraction

Smooth muscle contraction is a complex process vital for various bodily functions, from maintaining blood vessel tension to facilitating the movement of food through the digestive tract. Unlike striated muscles, smooth muscle contraction begins more slowly and lasts longer.
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...