NUPR1 modulates pulmonary embolism progression via smooth muscle cells phenotypic transformation

This study aimed to investigate the role of Nuclear Protein 1 (NUPR1) in pulmonary embolism (PE) and its impact on the phenotypic transformation of pulmonary artery smooth muscle cells (PASMCs).

A PE model was established via autologous pulmonary emboli infusion into the jugular vein. Partial Pressure of Oxygen (PaO2), Oxygenation Index (OI), Brain Natriuretic Peptide (BNP), and Troponin I (TnI) were measured, and lung tissue was subjected to hematoxylin-eosin (HE) staining. NUPR1 expression was assessed through Immunofluorescence and Western blot analyses. To investigate role of NUPR1, PE rats were treated with lentiviral vectors for NUPR1 knockdown (si-NUPR1) or overexpression (ov-NUPR1), and the effects on lung pathology were examined. NUPR1 expression was evaluated in human PASMCs. Additionally, PASMCs from SD rats were cultured under normoxic and hypoxic conditions to evaluate NUPR1 expression. Transfection of NUPR1 expression vectors into PASMCs allowed monitoring of phenotypic transformation-associated protein changes and PASMCs activity.

Increased NURP1 was observed in human-derived PASMCs. In PE rats, histological examination revealed ruptured pulmonary alveoli, exudate accumulation, interstitial edema, and infiltration of inflammatory cells, concomitant with elevated NUPR1 expression levels. Knockdown of NUPR1 in PE rats significantly improved lung tissue structure, reducing alveolar rupture and interstitial edema. Conversely, NUPR1 overexpression exacerbated lung damage, leading to increased inflammatory infiltration. NUPR1 expression in rat PASMCs remained stable under normoxic conditions; however, under hypoxic conditions, NUPR1 protein expression increased progressively over time. Subsequent upregulation of NUPR1 expression led to a decrease in the levels of contractile phenotype markers α-SMA and SM22α in PASMCs, accompanied by increased expression of synthetic phenotype markers Vimentin and OPN. This phenotypic shift was associated with enhanced cellular proliferation, invasion, and migration.

Elevated NUPR1 expression in PE exacerbates abnormal PASMCs proliferation by promoting their phenotypic transformation, thereby fostering the pathological progression of PE.