A long non-coding RNA H19/microRNA-138/TLR3 network is involved in high phosphorus-mediated vascular calcification...

Area of Science:

• Cardiovascular Biology
• Nephrology
• Molecular Biology

Background:

• Vascular calcification is a significant complication in chronic kidney disease (CKD), contributing to cardiovascular morbidity and mortality.
• High phosphorus levels are a key driver of vascular calcification in CKD patients.

Purpose of the Study:

• To investigate the molecular mechanisms underlying high phosphorus-induced vascular calcification in a rat model of CKD.
• To identify key molecular players, including long non-coding RNAs, in this pathological process.

Main Methods:

• Established a rat model of CKD using 5/6 nephrectomy.
• Administered normal phosphorus diet (NPD) or high phosphorus diet (HPD) to assess effects on kidney function and vascular health.
• Analyzed aortic tissues and vascular smooth muscle cells (VSMCs) for calcification, gene expression (RUNX2, α-SM actin, H19, miR-138, TLR3), and signaling pathway activation (NF-κB).

Main Results:

• High phosphorus diet (HPD) worsened kidney function, increased serum calcium, and induced vascular damage and calcification in the thoracic aorta.
• HPD upregulated H19, increased RUNX2, and decreased α-SM actin in aortic tissues and VSMCs.
• H19 was found to interact with miR-138, inhibiting its effect on TLR3 mRNA and activating the NF-κB pathway. Silencing H19 or TLR3 ameliorated calcification, while silencing miR-138 exacerbated it.

Conclusions:

• The H19/miR-138/TLR3 axis plays a critical role in high phosphorus-mediated vascular calcification in CKD.
• This molecular pathway, involving H19, miR-138, TLR3, and NF-κB, represents a potential therapeutic target for managing vascular calcification in CKD.