Hedgehog signaling is a potential therapeutic target for vascular calcification

Aoran Huang1, Lu Li1, Xiaoxu Liu1

  • 1Department of Nephrology, The First Hospital of China Medical University, Shenyang 110000, China.

Gene
|May 4, 2023
PubMed

Insights

Vascular calcification in chronic kidney disease is linked to Hedgehog signaling. Activating this pathway alleviated calcification, suggesting it as a potential therapeutic target.

Area of Science:

  • Cardiovascular Biology
  • Molecular Biology
  • Nephrology

Background:

  • Vascular calcification (VC) is a major cause of mortality in chronic kidney disease (CKD) patients.
  • Hedgehog (Hh) signaling is implicated in bone mineralization and cardiovascular diseases, but its role in VC is unclear.

Purpose of the Study:

  • To investigate the molecular mechanisms of VC in human primary vascular smooth muscle cells (VSMCs).
  • To explore the potential of targeting the Hh signaling pathway for VC treatment.

Main Methods:

  • Constructed a human VSMC calcification model and performed RNA sequencing.
  • Analyzed differentially expressed genes (DEGs), conducted enrichment and protein-protein interaction (PPI) network analyses.
  • Validated key genes and used Connectivity Map (CMAP) analysis to identify potential drugs, including Hh signaling modulators SAG and cyclopamine (CPN).

Main Results:

  • Identified 166 DEGs enriched in ossification, osteoblast differentiation, and Hh signaling pathways.
  • Discovered 10 key genes and identified potential therapeutic drugs.
  • In vitro, SAG treatment alleviated VSMC calcification, while CPN exacerbated it.

Conclusions:

  • VC pathogenesis is associated with Hh signaling.
  • Targeting the Hh signaling pathway offers a promising therapeutic strategy for VC.
Abstract

Related Concept Videos

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
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...
4.3K
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...
2.1K
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
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
8.8K