CD133+ progenitor cells promote pulmonary hypertension through CXCR4 signaling

Pulmonary hypertension (PH) is a condition marked by changes in the pulmonary vascular system and an increase in smooth muscle cells, but the specific progenitor cells involved in this process are not yet fully understood. Researchers investigated this by examining human PH lungs, experimental PH models, and using various laboratory techniques.

Through their analysis, they discovered that CD133 expression was significantly higher in both human and experimental PH lungs. When they examined the functions of these CD133+ cells, they found that they were involved in inflammatory, metabolic, chemokine-associated, and smooth muscle cell-like processes in PH lungs.

Furthermore, by using lineage tracing, they observed that CD133+ cells contributed to both endothelial and smooth muscle cell compartments during the development of experimental PH. They then proceeded to genetically remove CD133+ cells and found that this reduced the PH severity caused by hypoxia and the resulting pulmonary vascular remodeling. Additionally, deleting the CXCR4 gene in CD133+ cells further diminished the PH severity.

In conclusion, the researchers determined that CD133+ progenitor cells actively contribute to pulmonary vascular remodeling, and that CXCR4 signaling plays a crucial role in their pathogenic activity. The study suggests that targeting these pathogenic CD133+ cell states or the CXCL12/CXCR4 signaling pathway could be an effective strategy to limit vascular remodeling in PH patients.