https://scholars.lib.ntu.edu.tw/handle/123456789/621144
標題: | Sirolimus Suppresses Phosphorylation of Cofilin and Reduces Interstitial Septal Thickness in Sporadic Lymphangioleiomyomatosis | 作者: | YEN-LIN HUANG Chen, Po-Ru Lai, Ying-Ju HSAO-HSUN HSU |
關鍵字: | interstitial septal thickness; lymphangioleiomyomatosis; mTOR; p-cofilin; sirolimus | 公開日期: | 9-八月-2021 | 出版社: | MDPI | 卷: | 22 | 期: | 16 | 來源出版物: | International journal of molecular sciences | 摘要: | Sporadic lymphangioleiomyomatosis (S-LAM) is a rare lung disease characterized by the proliferation of smooth muscle-like LAM cells and progressive cystic destruction. Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has a proven efficacy in patients with LAM. However, the therapeutic mechanisms of sirolimus in LAM remain unclear. We aimed to evaluate sirolimus-related lung parenchymal changes and the potential effect in LAM cells and modulating pathological cystic destruction. Lung specimens were examined for histopathological changes by HMB45 staining and compared the LAM patients treated with and without sirolimus. We detected the overexpression of mTOR, HMB45, and phosphorylation of cofilin (p-cofilin) in LAM patients. Sirolimus showed efficacy in patients with LAM, who exhibited a reduced expression of mTOR and p-cofilin as well as reduced interstitial septal thickness. In addition, sirolimus suppresses mTOR and p-cofilin, thus suppressing the migration and proliferation of LAM cells isolated from the patient's lung tissue. This study demonstrates that interstitial septal thickness, as determined by histological structural analysis. Sirolimus effectively reduced the expression of p-cofilin and interstitial septal thickness, which may be a novel mechanism by sirolimus. Moreover, we develop a new method to isolate and culture the LAM cell, which can test the possibility of medication in vitro and impact this current study has on the LAM field. The development of approaches to interfere with mTOR-cofilin1-actin signaling may result in an option for S-LAM therapy. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/621144 | ISSN: | 16616596 | DOI: | 10.3390/ijms22168564 |
顯示於: | 醫學系 |
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