Exosomal hsa-miR-299-3p from endothelium mediates high phosphorus-induced vascular calcification in mice model of CKD via phosphorylated JAK2/STAT5 pathway

Quick Facts

  • Publication title: Exosomal hsa-miR-299-3p from endothelium mediates high phosphorus-induced vascular calcification in mice model of CKD via phosphorylated JAK2/STAT5 pathway
  • Journal: Front Pharmacol
  • Year: 2026
  • DOI: 10.3389/fphar.2026.1752954
  • PMID/PMCID: 42038288; PMC13103977

Research overview

This study investigates the role of endothelial cells (ECs)-derived exosomal microRNAs in mediating osteogenic differentiation of vascular smooth muscle cells (VSMCs) under high phosphate (HP) conditions. The miR-299-3p/MARCH3/p-JAK2/STAT5 signaling axis represents a critical regulatory pathway in VC pathogenesis and offers a potential therapeutic target for this life-threatening complication of CKD.

Key findings

HP-stimulated ECs released Exos (HP-Exos) that were internalized by VSMCs and significantly promoted VC in both in vitro and in vivo models.

miRNA sequencing identified miR-299-3p as significantly upregulated in HP-Exos.

Functional studies demonstrated that exosomal miR-299-3p directly targeted membrane-associated RING-CH3 (MARCH3), leading to activation of the p-JAK2/STAT5 signaling pathway.

This cascade subsequently upregulated osteogenic markers and downregulated contractile marker, thereby promoting osteogenic differentiation of VSMCs.

Study design

A CKD-VC mouse model was established using a HP and high-adenine diet.

Exosomes (Exos) were isolated from ECs cultured under normal or HP conditions.

The effects of Exos on calcification of VSMCs were evaluated using in vitro co-culture systems and in vivo administration.

Echo Biotech Role

Echo Biotech contributed EV isolation and purification, EV characterization, miRNA profiling/sequencing and bioinformatic analysis.

Related platforms: Exoomics®

Related services and capabilities: EV Isolation & Purification, EV Basic Characterization (TEM/NTA/WB), EV miRNA Profiling / Sequencing

References

Original publication: Exosomal hsa-miR-299-3p from endothelium mediates high phosphorus-induced vascular calcification in mice model of CKD via phosphorylated JAK2/STAT5 pathway Frontiers in pharmacology. 2026. DOI: 10.3389/fphar.2026.1752954. PMID/PMCID: 42038288; PMC13103977.