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Background <p>Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disorder with poor prognosis. The mechanism of IPF is poorly understood, and hence effective treatments are lacking. Neuron navigator 2 (NAV2) plays a critical role in cell migration and a variety of autoimmune diseases. However, its role in IPF is still unclear. </p> Methods <p>Serum samples from IPF patients and healthy volunteers were collected and NAV2 was detected via ELISAs. Bleomycin (BLM) was used to establish a pulmonary fibrosis model in C57BL/6&#xa0;J mice. Adeno-associated virus (AAV6)-shRNA was used to knockdown NAV2. Serum and alveolar lavage fluid were collected and IL-6 and TNF-α were detected. The degree of alveolitis and pulmonary fibrosis were scored. NAV2, anti-alpha smooth muscle (α-SMA), and fibronectin were measured by immunohistochemistry and Western blotting. SiRNA-NAV2-treated and STAT3-inhibited MRC-5 cells were treated with transforming growth factor-β1 (TGF-β1). The expression of fibronectin, α-SMA STAT3, and NAV2 was determined by Western blotting.</p> Results <p>NAV2 levels were elevated in the IPF patients compared with the controls (<i>p</i> &lt; 0.05). NAV2 expression was elevated in the lung tissue of the BLM-treated mice compared with that in the control mice (<i>p</i> &lt; 0.05). When the mice were administered AAV6-shRNA-NAV2, fibrosis was alleviated and both fibronectin and α-SMA levels were reduced. TGF-β1 treatment increased the expression of STAT3 and NAV2 in MRC-5 cells. When the cells were transfected with siRNA-NAV2 or treated with a STAT3 inhibitor, fibronectin and α-SMA expression was reduced.</p> Conclusion <p>NAV2 signaling promotes the progression of pulmonary fibrosis. The STAT3/NAV2 axis has an important regulatory role in the TGF-β1-related epithelial–mesenchymal transition, which might provide a potential target for IPF treatment.</p>

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STAT3/NAV2 signaling promotes the progression of pulmonary fibrosis

  • 期刊论文

  • 发表日期：

    2025年5月4日

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  • Daiju Hu,
  • Xiaohua Zhang,
  • Dongsheng Wang,
  • Wang Xie

摘要

Background

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disorder with poor prognosis. The mechanism of IPF is poorly understood, and hence effective treatments are lacking. Neuron navigator 2 (NAV2) plays a critical role in cell migration and a variety of autoimmune diseases. However, its role in IPF is still unclear.

Methods

Serum samples from IPF patients and healthy volunteers were collected and NAV2 was detected via ELISAs. Bleomycin (BLM) was used to establish a pulmonary fibrosis model in C57BL/6 J mice. Adeno-associated virus (AAV6)-shRNA was used to knockdown NAV2. Serum and alveolar lavage fluid were collected and IL-6 and TNF-α were detected. The degree of alveolitis and pulmonary fibrosis were scored. NAV2, anti-alpha smooth muscle (α-SMA), and fibronectin were measured by immunohistochemistry and Western blotting. SiRNA-NAV2-treated and STAT3-inhibited MRC-5 cells were treated with transforming growth factor-β1 (TGF-β1). The expression of fibronectin, α-SMA STAT3, and NAV2 was determined by Western blotting.

Results

NAV2 levels were elevated in the IPF patients compared with the controls (p < 0.05). NAV2 expression was elevated in the lung tissue of the BLM-treated mice compared with that in the control mice (p < 0.05). When the mice were administered AAV6-shRNA-NAV2, fibrosis was alleviated and both fibronectin and α-SMA levels were reduced. TGF-β1 treatment increased the expression of STAT3 and NAV2 in MRC-5 cells. When the cells were transfected with siRNA-NAV2 or treated with a STAT3 inhibitor, fibronectin and α-SMA expression was reduced.

Conclusion

NAV2 signaling promotes the progression of pulmonary fibrosis. The STAT3/NAV2 axis has an important regulatory role in the TGF-β1-related epithelial–mesenchymal transition, which might provide a potential target for IPF treatment.