Pulmonary vascular disease & thromboembolism
PDZ-Binding Kinase, a Novel Regulator of Vascular Remodeling in Pulmonary Arterial Hypertension
Authors' conclusion
PBK is a newly described target for PAH that is upregulated in proliferating PA smooth muscle cells, where it contributes to proliferation through changes in cytokinesis and cell cycle dynamics to promote medial thickening, fibrosis, increased PA resistance, elevated right ventricular systolic pressure, right ventricular remodeling, and PH.
Study context
- Population
- Mouse and rat models of pulmonary hypertension (PH) and human pulmonary arterial hypertension (PAH) (lung and isolated pulmonary arteries (PA))
- Outcome
- Role of PBK in PA remodeling in PH
Main finding
As reported in the abstract
- PBK upregulated in multiple models and species including humans
- PBK robustly upregulated in medial layer of PA, overlapping smooth muscle cell markers
- Active PBK increases PA smooth muscle cell proliferation; silencing, dominant negative PBK and pharmacological inhibitors reduce proliferation
- Pharmacological PBK inhibitors effective in PH reversal in mouse and rat models
- CRISPR/Cas9 PBK knockout in rats prevented development of PH
- PBK binds PRC1; active PBK increased PRC1 phosphorylation and supported cytokinesis; silencing or dominant negative PBK reduced cytokinesis and G2/M cells
Original publication
PDZ-Binding Kinase, a Novel Regulator of Vascular Remodeling in Pulmonary Arterial Hypertension. Circulation. Published 29 April 2024. doi:10.
Summarised from the published abstract; every number is checked against it