AMPK介导的自噬和线粒体自噬在咪喹莫特诱导的银屑病小鼠模型中的作用
The roles of AMPK-mediated autophagy and mitochondrial autophagy in a mouse model of imiquimod-induced psoriasis.
作者信息
Shen Hui, Sha Yan, Huang Jun, Mao An-Qi, Zhang Tao, Wu Mu-Yao, Sun Fang, Yu Ying-Yuan, Cheng Zhong-Qin, Gong Ya-Ting
机构信息
Department of Dermatology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine Zhangjiagang 215600, Jiangsu, China.
Department of Acupuncture, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine Zhangjiagang 215600, Jiangsu, China.
出版信息
Am J Transl Res. 2021 Nov 15;13(11):12626-12637. eCollection 2021.
BACKGROUND
Psoriasis is a systemic inflammatory disease characterized by epidermal hyperplasia and skin inflammatory infiltrates. Inactivation of AMPK has been shown to decrease autophagy, thereby inhibiting elimination of inflammatory factors and harmful substances, and aggravating psoriasis. However, the molecular mechanism through which AMPK affects psoriasis remains to be further explored. In this study, we investigated whether AMPK regulates autophagy through the ULK1/Atg7 signaling pathway and regulates mitochondrial autophagy through the PINK1/Parkin signaling pathway, thereby affecting a mouse model of psoriasis.
METHODS
Imiquimod was used to induce psoriasis-like lesions on the backs of mice. The severity of skin lesions in psoriatic mice was evaluated with the skin inflammation severity score, and epidermal thickness was measured on the basis of H&E staining. RT-PCR, western blotting and immunofluorescence staining were used to detect indicators of autophagy and mitochondrial autophagy.
RESULTS
AMPK activity was inhibited in the psoriasis mouse model, the autophagy-associated proteins ULK1/Atg7 were inhibited, and the mitochondrial autophagy proteins PINK1/Parkin were also decreased. Results indicated that autophagy and mitochondrial autophagy were inhibited in the mouse model. When AMPK signaling was upregulated, ULK1/Atg7 and PINK1/Parkin were upregulated, autophagy and mitochondrial autophagy increased, and skin lesions in the mouse model were alleviated. ULK1/Atg7 and PINK1/Parkin were down-regulated when AMPK signaling was downregulated, and psoriasis-like skin lesions were aggravated in mice. These results indicated that AMPK regulates autophagy through the ULK1/Atg7 signaling pathway and regulates mitochondrial autophagy through the PINK1/Parkin signaling pathway, thus affecting the prognosis of psoriasis in the mouse model.
CONCLUSION
AMPK affects the prognosis of psoriasis in a mouse model by regulating autophagy and mitochondrial autophagy.
背景
银屑病是一种以表皮增生和皮肤炎症浸润为特征的系统性炎症性疾病。已有研究表明，AMPK失活会降低自噬，从而抑制炎症因子和有害物质的清除，加重银屑病。然而，AMPK影响银屑病的分子机制仍有待进一步探索。在本研究中，我们探究了AMPK是否通过ULK1/Atg7信号通路调节自噬，并通过PINK1/Parkin信号通路调节线粒体自噬，从而影响银屑病小鼠模型。
方法
使用咪喹莫特诱导小鼠背部出现银屑病样病变。用皮肤炎症严重程度评分评估银屑病小鼠皮肤病变的严重程度，并基于苏木精-伊红染色测量表皮厚度。采用逆转录聚合酶链反应（RT-PCR）、蛋白质免疫印迹法和免疫荧光染色检测自噬和线粒体自噬指标。
结果
在银屑病小鼠模型中，AMPK活性受到抑制，自噬相关蛋白ULK1/Atg7受到抑制，线粒体自噬蛋白PINK1/Parkin也减少。结果表明，该小鼠模型中的自噬和线粒体自噬受到抑制。当AMPK信号上调时，ULK1/Atg7和PINK1/Parkin上调，自噬和线粒体自噬增加，小鼠模型中的皮肤病变得到缓解。当AMPK信号下调时，ULK1/Atg7和PINK1/Parkin下调，小鼠中银屑病样皮肤病变加重。这些结果表明，AMPK通过ULK1/Atg7信号通路调节自噬，并通过PINK1/Parkin信号通路调节线粒体自噬，从而影响银屑病小鼠模型的预后。
结论
AMPK通过调节自噬和线粒体自噬影响银屑病小鼠模型的预后。
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