Placenta growth factor (PlGF) triggers small airway remodeling (SAR) in chronic obstructive pulmonary disease (COPD)

Abstract

COPD is predicted to become the third leading cause of death worldwide by 2030. So far, the detailed pathogenic mechanisms of COPD are not fully understood. The cigarette smoke (CS)-trigger protease-antiprotease imbalance and chronic inflammation are crucial pathogenic mechanisms of COPD-associated SAR. CS-induced chronic inflammation is thought to be responsible for SAR. However, anti-inflammatory strategy fails to ameliorate the progression of CS-induced SAR. We proved other than CS-induced chronic inflammation, the excessive elastases upregulated PlGF, a VEGF family protein promotes angiogenesis in embryonic stage, triggers alveolar epithelial cell autophagy, apoptosis and pulmonary emphysema in mice. Whether PlGF is a pathological factor for CS-induced SAR beyond chronic inflammation is needed further investigation. Firstly, we demonstrate COPD-associated elastase, neutrophil elastase and matrix metalloproteinases-12 increased PlGF expression in lung epithelial cells. We had validated ablation of PlGF decreases the CS-induced collagen deposition in mice small airway by Masson stain (Fig. 1). Furthermore, the results of Western blot assay indicated PlGF increases mesenchymal transition markers expression but decreased epithelial markers expression. We conclude COPD-associated elastases-upregulated PlGF may play a crucial rule in CS-induced SAR progression.