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| Glypican3-WNT-JNK pathway mediates the molecular mechanism of local cell inflammation in lung induced by lipopolysaccharide |
| CHEN Chaolei1, lin Yuting1, ZHANG Sangsang1, SONG Chenjian1, HE Fei2, DONG Li1, CHEN Junjie1, WANG Beibei1, DONG Nian1, LI Yuping1, CHEN Chengshui1 |
| 1.Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China; 2.Department of Cardiovascular Medicine, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou 325000, China |
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| Cite this article: |
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CHEN Chaolei,lin Yuting,ZHANG Sangsang, et al. Glypican3-WNT-JNK pathway mediates the molecular mechanism of local cell inflammation in lung induced by lipopolysaccharide[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2019, 49(10): 703-711.
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Abstract Objective: To investigate the important role of (glypican-3) GPC3 in lipopolysaccharide (LPS)-induced microenvironment of local inflammation in airway epithelial cells, and to further investigate the GPC3-WNT pathway molecular mechanism of LPS-induced local inflammation in the lung. Methods: The expression of GPC3 in alveolar lavage and lung tissue and its expression location were detected in an ALI mouse model simulated by LPS airway aspiration. Cultured human lung 16HBE cells were stimulated by LPS to establish acute inflammatory cells. The mRNA expressions of GPC3, TNF-α and TGF-β were detected by RT-PCR, meanwhile the expressions of GPC3, TNF-α and TGF-β proteins were assessed by Western Blot. The expression of inflammatory cytokines TNF-α and TGF-β was detected in 16HBE cells stimulated by exogenous GPC3. Cells were treated with GPC3-WNT pathway inhibitor at different concentrations, then expression levels of TNF-α and TGF-β were measured by the above-mentioned methods. Results: GPC3 expression showed a significant increase in ALI mouse model induced by LPS. In addition, increased expression of GPC3 was also observed in LPS in vitro. Meanwhile, exogenous GPC3 protein stimulated bronchial epithelial cells to produce a variety of inflammatory factors, which may indicate that GPC3 has pro-inflammatory effect. Additionally, the production of inflammatory cytokines in bronchial epithelial cell induced by GPC3 was blocked by inhibitors of the WNT-JNK pathway, suggesting that GPC3 involved in the potential signaling pathway in local lung cells during ALI/ARDS. Conclusion: There is a linear signal pathway, GPC3-WNT-JNK, in the process of LPS stimulating bronchial epithelial cells. This discovery may provide a new molecular target and molecular mechanism for the treatment of ALI/ARDS.
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Received: 11 January 2019
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