丝裂霉素C诱导人气管成纤维细胞自噬并抑制其生长

IF 1.7 4区医学 Q2 OTORHINOLARYNGOLOGY

Laryngoscope Investigative Otolaryngology Pub Date : 2025-10-16 DOI:10.1002/lio2.70251

Jeong-Mi Kim, Sungryeal Kim, Eun-Jeong Jeon, Jin-Mi Park, Seo-Young Park, Jeong-Seok Choi

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引用次数: 0

摘要

目的丝裂霉素C （Mitomycin C， MMC）常用于预防气管狭窄术后纤维化，但其确切的细胞机制尚不清楚。本研究旨在阐明MMC对正常人气管成纤维细胞（hTF）和人支气管/气管上皮细胞（hTEC）的细胞毒性和自噬作用，以更好地了解其在纤维化调节中的潜在作用。方法hTF和hTEC分别于浓度为0.01、0.1和1 μg/mL的MMC中暴露24、48和72 h。细胞增殖、自噬诱导和自噬相关蛋白的表达通过活力测定和Western blot分析进行评估。此外，我们还研究了MMC对细胞迁移和成纤维细胞向肌成纤维细胞转化的影响。结果MMC部分抑制hTEC增殖，但不诱导自噬。相反，MMC在促进自噬的同时，以剂量和时间依赖的方式显著抑制hTF的生长。Western blot分析显示，mmc处理的hTF中LC3、ATG5和Rab7的表达增加，同时cyclin D1水平降低。此外，MMC还能减弱tgf β诱导的成纤维细胞中α - sma的表达，提示其对纤维化相关的细胞转化具有抑制作用。结论MMC通过自噬介导的细胞死亡抑制人气管成纤维细胞增殖，同时保留上皮细胞。这种双重作用强调了其作为气管狭窄治疗的靶向抗纤维化药物的潜力。需要进一步的研究来优化MMC的应用，并阐明其对气道重塑的长期影响。证据等级

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Mitomycin C Induces Autophagy in Human Tracheal Fibroblasts and Suppresses Their Growth

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Mitomycin C Induces Autophagy in Human Tracheal Fibroblasts and Suppresses Their Growth

Objective

Mitomycin C (MMC) is frequently used to prevent postoperative fibrosis in tracheal stenosis, yet its precise cellular mechanisms remain inadequately understood. This study aimed to elucidate the cytotoxic and autophagic effects of MMC on normal human tracheal fibroblasts (hTF) and human bronchial/tracheal epithelial cells (hTEC) to better understand its potential role in fibrosis regulation.

Methods

hTF and hTEC were exposed to MMC at concentrations of 0.01, 0.1, and 1 μg/mL for 24, 48, and 72 h. Cell proliferation, autophagy induction, and the expression of autophagy-related proteins were assessed using viability assays and Western blot analysis. Additionally, the effects of MMC on cell migration and fibroblast-to-myofibroblast transition were investigated.

Results

MMC partially reduced hTEC proliferation without inducing autophagy. In contrast, MMC significantly suppressed hTF growth in a dose- and time-dependent manner while promoting autophagy. Western blot analysis revealed increased expression of LC3, ATG5, and Rab7 in MMC-treated hTF, along with reduced cyclin D1 levels. Furthermore, MMC attenuated TGFβ-induced αSMA expression in fibroblasts, suggesting an inhibitory effect on fibrosis-related cellular transformation.

Conclusion

These findings indicate that MMC suppresses human tracheal fibroblast proliferation through autophagy-mediated cell death while sparing epithelial cells. This dual effect underscores its potential as a targeted antifibrotic agent for tracheal stenosis management. Further research is needed to optimize MMC's application and elucidate its long-term impact on airway remodeling.