Related Experiment Video

Updated: Jul 23, 2025

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

19.6K

Shh-Gli2-Runx2 inhibits vascular calcification

Aoran Huang1, Tianhua Xu1, Xiaomei Lu2

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

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
|July 14, 2023
PubMed

Insights

Shh signaling, a key pathway in bone formation, was found to be decreased in vascular calcification (VC). Restoring Shh levels inhibited VC, suggesting Shh as a potential therapeutic target for this condition.

Area of Science:

  • Cardiovascular Biology
  • Renal Medicine
  • Molecular Biology

Background:

  • Vascular calcification (VC) is a common complication in chronic kidney disease (CKD) and significantly increases mortality risk.
  • Shh, a ligand in Hedgehog (Hh) signaling, is involved in osteogenesis and cardiovascular diseases, but its role in VC remains unexplored.

Purpose of the Study:

  • To investigate the role of Shh signaling in the development of vascular calcification (VC) in chronic kidney disease (CKD).
  • To explore Shh as a potential therapeutic target for treating VC.

Main Methods:

  • Vascular smooth muscle cells (VSMCs) were induced to calcify using inorganic phosphorus.
  • Vascular calcification (VC) was induced in mice using an adenine diet supplemented with phosphorus.
  • Shh signaling pathway modulation was achieved using agonists (SAG) and antagonists (CPN), and gene manipulation (overexpression/silencing) of Shh and Gli2.

Main Results:

  • Shh levels were reduced in calcified VSMCs, arteries of mice with VC, and radial arteries of CKD patients with VC.
  • Shh overexpression inhibited VSMC calcification, while Shh silencing accelerated it.
  • Hedgehog signaling agonist (SAG) alleviated VC, whereas antagonist (CPN) worsened it.
  • Shh inhibited VC via Gli2, which promoted Runx2 degradation, independent of Smurf1 and Cullin4B.

Conclusions:

  • Shh signaling plays a protective role against vascular calcification (VC).
  • The study elucidates the mechanism of Shh in preventing VC through Gli2-mediated Runx2 degradation.
  • Shh emerges as a promising therapeutic target for managing vascular calcification in CKD.
Abstract

Keywords:
Sonic hedgehogchronic kidney diseaseubiquitin proteasomal degradationvascular calcificationvascular smooth muscle cells

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