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miR-205-5p通过肺细胞外囊泡参与介导煤工尘肺相关性结节性甲状腺疾病的发生发展。

Involvement of miR-205-5p in mediating the development of nodular thyroid disease associated with coal worker's pneumoconiosis via pulmonary extracellular vesicles.

作者信息

Zhao Feng, Hao Yu, Zhang Hongzhen

机构信息

Thyroid and Breast Surgery Department, The First Hospital of Anhui University of Science and Technology, Huainan First People's Hospital, Huainan, China.

Breast Surgery, Provincial Hospital of Weihai City, Weihai, Shandong, China.

出版信息

Front Endocrinol (Lausanne). 2025 Jul 4;16:1528330. doi: 10.3389/fendo.2025.1528330. eCollection 2025.

Abstract

OBJECTIVE

Coal worker's pneumoconiosis (CWP) is an occupational disease, and the mechanisms underlying the development of its complication, nodular thyroid disease (NTD), remain unclear. This study aimed to investigate the role of miR-205-5p (miR-205-5p) in the development of nodular thyroid disease associated with coal worker's pneumoconiosis.

METHODS

The potential role of pulmonary extracellular vesicles in triggering coal worker's pneumoconiosis-associated nodular thyroid disease was explored. RNA was extracted from isolated extracellular vesicle samples, and real-time fluorescent quantitative RT-qPCR was performed using specific primers and probes. The levels of miR-205-5p in the extracellular vesicles from the supernatant of each treatment group were compared, and the significant expression of miR-205-5p in the extracellular vesicles was detected by RT-qPCR to evaluate the regulatory role of lung-derived extracellular vesicles in the development of coal worker's pneumoconiosis-associated nodular thyroid disease. In addition, cell proliferation, apoptosis, and invasion capabilities were assessed using the CCK-8 assay for cell proliferation activity, Annexin V-FITC/PI double staining and flow cytometry for cell apoptosis rate, and Transwell assay for cell invasion ability.

RESULTS

By isolating, purifying, and analyzing extracellular vesicles from coal worker's pneumoconiosis patients and healthy controls, it was found that the expression of miR-205-5p in the plasma of coal worker's pneumoconiosis patients was significantly higher than that in the healthy controls (<0.01). Furthermore, the expression levels of ATF4 and CHOP were also significantly increased in coal worker's pneumoconiosis patients (<0.01), consistent with the expression trend of miR-205-5p. Further cell experiments demonstrated that miR-205-5p can promote the proliferation and formation of nodules in thyroid cells by regulating the expression of downstream target genes. This study revealed the critical role of miR-205-5p in the development of nodular thyroid disease associated with coal worker's pneumoconiosis and provided new experimental evidence for the diagnosis and treatment of this disease.

CONCLUSION

miR-205-5p in pulmonary extracellular vesicles mediates the development of nodular thyroid disease associated with coal worker's pneumoconiosis through the ATF4/CHOP signaling axis. Further research is essential to comprehensively investigate the specific targets through which miR-205-5p derived from pulmonary extracellular vesicles triggers the development of nodular thyroid disease associated with coal worker's pneumoconiosis via the ATF4/CHOP signaling axis.

摘要

目的

煤工尘肺(CWP)是一种职业病,其并发症结节性甲状腺疾病(NTD)的发病机制尚不清楚。本研究旨在探讨miR-205-5p在煤工尘肺相关结节性甲状腺疾病发生发展中的作用。

方法

探讨肺细胞外囊泡在引发煤工尘肺相关结节性甲状腺疾病中的潜在作用。从分离的细胞外囊泡样本中提取RNA,并使用特异性引物和探针进行实时荧光定量RT-qPCR。比较各治疗组上清液中细胞外囊泡中miR-205-5p的水平,并通过RT-qPCR检测细胞外囊泡中miR-205-5p的显著表达,以评估肺源性细胞外囊泡在煤工尘肺相关结节性甲状腺疾病发生发展中的调节作用。此外,使用CCK-8法检测细胞增殖活性、Annexin V-FITC/PI双染和流式细胞术检测细胞凋亡率、Transwell法检测细胞侵袭能力,评估细胞增殖、凋亡和侵袭能力。

结果

通过对煤工尘肺患者和健康对照者的细胞外囊泡进行分离、纯化和分析,发现煤工尘肺患者血浆中miR-205-5p的表达显著高于健康对照者(<0.01)。此外,煤工尘肺患者中ATF4和CHOP的表达水平也显著升高(<0.01),与miR-205-5p的表达趋势一致。进一步的细胞实验表明,miR-205-5p可通过调节下游靶基因的表达促进甲状腺细胞的增殖和结节形成。本研究揭示了miR-205-5p在煤工尘肺相关结节性甲状腺疾病发生发展中的关键作用,为该疾病的诊断和治疗提供了新的实验依据。

结论

肺细胞外囊泡中的miR-205-5p通过ATF4/CHOP信号轴介导煤工尘肺相关结节性甲状腺疾病的发生发展。进一步研究全面探究肺细胞外囊泡来源的miR-205-5p通过ATF4/CHOP信号轴触发煤工尘肺相关结节性甲状腺疾病发生发展的具体靶点至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44ed/12271885/a9938daed758/fendo-16-1528330-g001.jpg

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