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Updated: Sep 14, 2025
A Mouse Model of Pulmonary Fibrosis Induced by Nasal Bleomycin Nebulization
Published on: January 20, 2023
SZ168 alleviates bleomycin-induced pulmonary fibrosis by inhibiting podoplanin-induced platelet activation
Xue Gao1, Yao-Xin Chen1, Shi Wu2
1Department of Respiratory and Critical Care Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou 215000, China.
Background:
Idiopathic pulmonary fibrosis (IPF) is a serious chronic lung disease characterized by progressive dyspnea and deterioration of lung function. According to existing observations, platelet activation and fibroblast-myofibroblast differentiation plays an important role in the development of IPF. This study aimed to investigate the role of podoplanin (PDPN) in this differentiation process during IPF progression. Specifically, the article explores PDPN expression in human IPF and bleomycin (BLM)-induced pulmonary fibrosis in mice, along with the effects and mechanisms of the PDPN monoclonal antibody SZ168 on pulmonary fibrosis both in vitro and in vivo.
Methods:
Data analysis of human IPF datasets to identify PDPN as a differentially expressed gene. Following this, in vivo and in vitro experiments were conducted to investigate the role and underlying mechanisms of PDPN in the progression of IPF. Additionally, we measured PDPN levels in the serum of IPF patients to validate its differential expression.
Results:
Our findings show that PDPN is highly expressed in IPF patients. Additionally, PDPN expression is elevated in TGF-β1-induced fibroblasts and in the lungs of bleomycin-induced mouse models. We particularly found that PDPN was expressed in WI-38 human pulmonary fibroblasts. Knockdown of PDPN in fibroblasts suppresses TGF-β-induced differentiation into myofibroblasts. Furthermore, the PDPN monoclonal antibody SZ168 inhibits platelet-induced fibroblast differentiation. Mechanistic analysis reveals that PDPN promotes bleomycin-induced pulmonary fibrosis via the activation of the RhoA/ROCK signaling pathway.
Conclusions:
PDPN is significantly upregulated in the pathogenesis of idiopathic pulmonary fibrosis (IPF), and closely associated with the differentiation of fibroblasts into myofibroblasts. The monoclonal antibody SZ168 effectively inhibits platelet activation, thereby inhibiting the differentiation of fibroblasts induced by PDPN and mitigating the progression of pulmonary fibrosis.
