Related Experiment Video
Updated: Jun 29, 2025
A Semi-Automated and Reproducible Biological-Based Method to Quantify Calcium Deposition In Vitro
Published on: June 2, 2022
Hypoxia-Inducible Factor-1α Regulates High Phosphate-Induced Vascular Calcification via Type III Sodium-Dependent
Chengkun Guo1, Zhengli Quan1, Jingjing Ke1
1Nephrology Department, Jingmen Central Hospital Affiliated to Hubei Minzu University, Jingmen, Hubei 448000, China.
Insights
Hypoxia-inducible factor-1 alpha (HIF-1α) drives vascular calcification by upregulating phosphate transporter 1 (Pit-1). Targeting HIF-1α and Pit-1 offers a potential treatment for high phosphate-induced vascular calcification.
Area of Science:
- Cardiovascular Biology
- Nephrology
- Molecular Medicine
Background:
- Vascular calcification (VC) is a common complication in chronic kidney disease patients, posing a significant public health challenge.
- Hypoxia-inducible factor-1 alpha (HIF-1α) is implicated in high phosphate-induced VC, but its precise mechanism and therapeutic targets remain unclear.
Purpose of the Study:
- To elucidate the underlying mechanism of HIF-1α in high phosphate-induced VC.
- To investigate the role of phosphate transporter 1 (Pit-1) in HIF-1α-mediated VC.
- To identify potential therapeutic targets for high phosphate-induced VC.
Main Methods:
- Human aortic smooth muscle cells (HASMCs) were cultured under high phosphate conditions.
- HIF-1α expression was manipulated using small interfering RNA and overexpression plasmids.
- Pit-1 function was inhibited using phosphonoformic acid.
- Expression of HIF-1α, Pit-1, Runx2, and SM22α was assessed; calcium content and cell viability were measured.
Main Results:
- High phosphate upregulated HIF-1α and Pit-1, induced calcium deposition, and altered phenotypic markers (Runx2, SM22α) in HASMCs.
- HIF-1α suppression attenuated Pit-1 expression, calcium deposition, and phenotypic changes.
- Inhibition of Pit-1 function prevented VC, even with HIF-1α overexpression.
Conclusions:
- HIF-1α promotes high phosphate-induced VC by upregulating Pit-1 expression.
- The pro-calcifying effect of HIF-1α is mediated through Pit-1.
- HIF-1α and Pit-1 represent promising therapeutic targets for managing high phosphate-induced vascular calcification.
Abstract:
Vascular calcification (VC) has a high incidence in patients with chronic kidney disease, which is a worldwide public health problem and presents a heavy burden to society. Hypoxia-inducible factor (HIF)-1α, the active subunit of HIF-1, has been reported to play a vital role in high phosphate-induced VC. However, the underlying mechanism is still undetermined, and effective treatment is unavailable. In the present study, human aortic smooth muscle cells (HASMCs) were cultured under normal or high phosphate media conditions. HIF-1α small interfering RNA and overexpression plasmids were employed to regulate HIF-1α expression. Phosphonoformic acid was employed to restrain the function of type III sodium-dependent phosphate cotransporter 1 (Pit-1). The expression levels of HIF-1α, Pit-1, runt-related transcription factor 2 (Runx2), and smooth muscle 22 alpha (SM22α) were evaluated, and the calcium contents were also examined. Cell growth was assessed using an MTT assay. High phosphate stimulation caused an upregulation in HIF-1α and Pit-1 expression levels and induced calcium depositions in HASMCs. Upregulation of Runx2 expression accompanied by downregulation of SM22α expression was observed in the high phosphate group. Following the suppression of HIF-1α expression, there was a concomitant attenuation in Pit-1 expression, calcium deposition, the alteration of phenotypic transition marker genes, and vice versa. The most serious calcium deposition was noted in HASMCs cultured under high phosphate conditions which were pretreated with a HIF-1α overexpression plasmid. However, when the biological functions of Pit-1 were restrained, the putative serious calcium deposition was not formed even in HASMCs transfected with a HIF-1α overexpression plasmid. The findings confirmed that HIF-1α regulated Pit-1 expression and exerted its pro-calcifying effect through Pit-1, which identified HIF-1α and Pit-1 as therapeutic targets for high phosphate-induced VC.
More Related Videos
08:43Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
14:55Analysis of Minerals Produced by hFOB 1.19 and Saos-2 Cells Using Transmission Electron Microscopy with Energy Dispersive X-ray Microanalysis
Published on: June 24, 2018
Related Concept Videos
01:24Regulation of Angiogenesis and Blood Supply
01:27Roles of Electrolytes: Calcium and Phosphate
The calcium concentration in blood plasma is primarily...
01:42Phosphoinositides and PIPs
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
01:17Hormones and Bone Tissue
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
02:54Protein Kinases and Phosphatases
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
01:58Cell Specific Gene Expression