SerpinB1a may drive progression through CTSG-linked and pulmonary microvascular dysfunction.
Evidence
Human serum association, CBDL-induced rat HPS knockdown experiments, and PMVEC cell assays linked elevated SerpinB1a to lower arterial oxygen saturation, pulmonary hemorrhage and microvascular dilation, angiogenic cell behavior, and CTSG/VEGF/AMPK/mTOR-mediated mitophagy.
Caveat
The human evidence is correlative, while the intervention and mechanism data come from rat and cell models rather than clinical SerpinB1a targeting.
Simplified
, as an important mechanism for selective removal of damaged mitochondria in cells, plays a crucial role in upholding cellular homeostasis. Mounting evidence suggests that autophagy is associated with lung disease. However, the potential molecular mechanisms affecting mitophagy are still obscure in (HPS) development. In this study, elevated SerpinB1a levels were detected in HPS patients' serum, showing a significant inverse correlation with arterial oxygen saturation. In the CBDL-induced rat HPS model, SerpinB1a knockdown attenuated pulmonary hemorrhage, microvascular dilation, and hepatic fibrosis. In vitro studies demonstrated that treatment of PMVECs with serum from HPS rats induced pathological proliferation, migration, and angiogenesis. Silencing of SerpinB1a effectively suppressed these aberrant cellular processes. Mechanistically, SerpinB1a promoted PMVEC dysfunction by interacting with and upregulating Cathepsin G (CTSG), thus activating the VEGF / AMPK / mTOR pathway and subsequent induction of mitophagy. In conclusion, SerpinB1a knockdown attenuated pulmonary microvascular dilation and HPS progression by inhibiting this CTSG/VEGF/AMPK/mTOR axis. These findings elucidate the mechanistic role of SerpinB1a in HPS progression and suggest its potential as a novel therapeutic target for HPS.
Key numbers
15 of 15 patients
Level Increase
All patients exhibited elevated levels.
49.29±9.25 years
Age Comparison
Mean age of patients enrolled in the study.
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