Related Experiment Video

Updated: Jun 25, 2025

Isolation of Mouse Interstitial Valve Cells to Study the Calcification of the Aortic Valve In Vitro
05:47

Isolation of Mouse Interstitial Valve Cells to Study the Calcification of the Aortic Valve In Vitro

Published on: May 10, 2021

4.0K

FOXO1 regulates RUNX2 ubiquitination through SMURF2 in calcific aortic valve disease

Chen Jiang1, Dingyi Yao1, Zongtao Liu1

  • 1Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.

Redox Biology
|May 29, 2024
PubMed

Insights

Forkhead box O1 (FOXO1) is down-regulated in calcific aortic valve disease (CAVD), promoting valve calcification by stabilizing RUNX2. Targeting the FOXO1/SMURF2/RUNX2 pathway may offer new therapies for CAVD.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Pathogenesis of Valve Disease

Background:

  • Calcific aortic valve disease (CAVD) is prevalent with no current medical treatments.
  • Forkhead box O1 (FOXO1) is implicated in cardiovascular diseases, but its role in CAVD is unclear.

Purpose of the Study:

  • To elucidate the specific role of FOXO1 in the pathogenesis of CAVD.
  • To identify potential therapeutic targets for CAVD based on FOXO1's function.

Main Methods:

  • Analysis of clinical specimens and GEO database to assess FOXO1 expression in CAVD.
  • In vitro experiments involving FOXO1 silencing in valve interstitial cells (VICs).
  • In vivo studies using Apoe-/- mice to evaluate the impact of FOXO1 inhibition on aortic valve calcification.

Main Results:

  • FOXO1 was significantly downregulated in VICs from calcified aortic valves.
  • FOXO1 silencing or inhibition accelerated VIC osteogenic differentiation and aortic valve calcification.
  • FOXO1 promotes RUNX2 ubiquitination and degradation, mediated by SMURF2.

Conclusions:

  • A novel mechanism involving the FOXO1/SMURF2/RUNX2 axis in CAVD pathogenesis was uncovered.
  • FOXO1 or SMURF2 modulation presents a potential therapeutic strategy to inhibit CAVD progression.
Keywords:
Calcific aortic valve diseaseForkhead box O1PhosphorylationSMAD-Specific E3 ubiquitin ligase 2Ubiquitination

More Related Videos

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation08:43

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

Published on: May 31, 2016

19.5K
Isolation and Characterization of Primary Rat Valve Interstitial Cells: A New Model to Study Aortic Valve Calcification08:55

Isolation and Characterization of Primary Rat Valve Interstitial Cells: A New Model to Study Aortic Valve Calcification

Published on: November 20, 2017

9.8K

Related Concept Videos

Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.6K
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...
7.3K
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
892
Cis-regulatory Sequences02:02

Cis-regulatory Sequences

Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
9.9K
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...
7.3K