Inhibition of lung microbiota-derived proapoptotic peptides ameliorates acute exacerbation of pulmonary fibrosis.
Inhibition of lung microbiota-derived proapoptotic peptides ameliorates acute exacerbation of pulmonary fibrosis.
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DOI：
10.1038/s41467-022-29064-3
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发表时间：
2022-03-23
影响因子：
16.6
通讯作者：
Gabazza EC
中科院分区：
文献类型：
--
作者：
D'Alessandro-Gabazza CN;Yasuma T;Kobayashi T;Toda M;Abdel-Hamid AM;Fujimoto H;Hataji O;Nakahara H;Takeshita A;Nishihama K;Okano T;Saiki H;Okano Y;Tomaru A;Fridman D'Alessandro V;Shiraishi M;Mizoguchi A;Ono R;Ohtsuka J;Fukumura M;Nosaka T;Mi X;Shukla D;Kataoka K;Kondoh Y;Hirose M;Arai T;Inoue Y;Yano Y;Mackie RI;Cann I;Gabazza EC
特发性肺纤维化是一种病因不明的不治之症。特发性肺纤维化的急性加重与高死亡率相关。肺纤维化急性加重期肺上皮细胞过度凋亡。我们最近发现了Corisin，一种促凋亡的多肽，可以触发肺纤维化的急性加重。在这里，我们提供了洞察力的潜在机制的加工和释放的Corisin。此外，我们通过显著抑制人转化生长因子β-1模型中的急性加重和博莱霉素模型中的急性肺损伤，证明了抗菌素单抗通过显著抑制肺纤维化而改善肺纤维化。通过研究在急性肺损伤的一般模型中抗鸡冠菌素单抗的影响，我们进一步揭示了珊瑚草素影响这类疾病的潜力。这些结果强调了Corisin在肺纤维化急性加重和急性肺损伤的发病机制中的作用，并为治疗这种不治之症提供了一种新的方法。在这里，作者表明，使用针对肺微生物衍生的促凋亡多肽Corisin的单抗中和治疗可以改善小鼠肺纤维化的急性加重和内毒素诱导的急性肺损伤的严重程度。
Idiopathic pulmonary fibrosis is an incurable disease of unknown etiology. Acute exacerbation of idiopathic pulmonary fibrosis is associated with high mortality. Excessive apoptosis of lung epithelial cells occurs in pulmonary fibrosis acute exacerbation. We recently identified corisin, a proapoptotic peptide that triggers acute exacerbation of pulmonary fibrosis. Here, we provide insights into the mechanism underlying the processing and release of corisin. Furthermore, we demonstrate that an anticorisin monoclonal antibody ameliorates lung fibrosis by significantly inhibiting acute exacerbation in the human transforming growth factorβ1 model and acute lung injury in the bleomycin model. By investigating the impact of the anticorisin monoclonal antibody in a general model of acute lung injury, we further unravel the potential of corisin to impact such diseases. These results underscore the role of corisin in the pathogenesis of acute exacerbation of pulmonary fibrosis and acute lung injury and provide a novel approach to treating this incurable disease. Here, the authors show that treatment with a monoclonal neutralizing antibody against the lung microbiota-derived proapoptotic peptide corisin ameliorates acute exacerbation of pulmonary fibrosis and severity of endotoxin-induced acute lung injury in mice.
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通讯作者：
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