Expression, localization and anti-fibrotic effect of HSPG2 in idiopathic pulmonary fibrosis

Background Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by excessive pulmonary tissue fibrosis, and the role of pulmonary epithelial cells in its pathological process has attracted increasing attention. The heparan sulfate proteoglycan 2 (HSPG2, also known as perlecan) gene is involved in the regulation of various cellular functions, but its mechanism of action in IPF remains unclear. This study aimed to systematically investigate the expression characteristics, cellular localization and functional effects of HSPG2 in IPF. Methods Lung tissue samples from 8 clinical IPF patients were collected, and the expression of HSPG2 in epithelial cells was detected by immunohistochemistry and immunofluorescence. A bleomycin-induced mouse model of pulmonary fibrosis was established, and an in vitro fibrosis model was constructed by stimulating human pulmonary epithelial cells (A549, Beas-2b) with transforming growth factor beta 1 (TGF-β1). Results HSPG2 expression was significantly upregulated in lung tissues of IPF patients, lung tissues of fibrotic mice and human pulmonary epithelial cells stimulated with TGF-β1. TGF-β1 could induce the upregulation of fibronectin 1 (FN1) and alpha-smooth muscle actin (α-SMA) in human pulmonary epithelial cells, while HSPG2 silencing effectively inhibited the above effects and attenuated TGF-β1-induced cell proliferation and migration. Conclusions HSPG2 is highly expressed during pulmonary fibrosis, and its silencing can inhibit fibrotic activation, proliferation and migration of epithelial cells, suggesting that HSPG2 may play an important profibrotic role in IPF.