Elastase induced lung epithelial cell apoptosis and emphysema through placenta growth factor

Area of Science:

• Pulmonary Medicine
• Cell Biology
• Molecular Biology

Background:

• Chronic pulmonary obstructive disease (COPD) is a leading cause of death with unclear pathogenesis.
• Pulmonary emphysema, a key COPD component, involves oxidative stress, inflammation, protease imbalance, and lung epithelial (LE) cell apoptosis.
• Previous studies linked higher placenta growth factor (PlGF) levels in COPD patients and demonstrated PlGF's role in emphysema and LE cell apoptosis.

Purpose of the Study:

• To investigate if porcine pancreatic elastase (PPE) upregulates PlGF expression in LE cells.
• To determine if PlGF induces LE cell apoptosis and identify downstream signaling pathways.
• To explore the role of PlGF in PPE-induced emphysema.

Main Methods:

• In vivo and in vitro experiments using wild-type and PlGF knockout mice.
• Intratracheal instillation of PPE.
• Assessment of PlGF expression and secretion.
• Analysis of LE cell apoptosis.
• Investigation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) pathways.

Main Results:

• PPE significantly increased PlGF secretion and expression in LE cells, both in vivo and in vitro.
• PlGF induced LE cell apoptosis.
• PPE-induced emphysema in mice was dependent on PlGF.
• PlGF-induced LE cell apoptosis and PPE-induced emphysema were mediated by JNK and p38 MAPK activation.

Conclusions:

• PPE upregulates PlGF, which subsequently induces LE cell apoptosis through JNK and p38 MAPK pathways, contributing to emphysema development.
• Elevated PlGF and its downstream signaling pathways are implicated in PPE-induced emphysema.
• Targeting PlGF and its signaling pathways presents a potential therapeutic strategy for COPD.