Chen Xu, Li Li, Xu Song, Bu Wenbo, Chen Kun, Li Min, Gu Heng
Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Science, Peking Union Medical College, Nanjing, China.
Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Science, Peking Union Medical College, Nanjing, China.
J Photochem Photobiol B. 2018 Jan;178:152-164. doi: 10.1016/j.jphotobiol.2017.08.043. Epub 2017 Sep 4.
Autophagy is a self-digestive pathway that helps to maintain cellular homeostasis, and many autophagy-related gene (ATG)s involved the regulation of the autophagy process. Ultraviolet light is a common stressor of skin, but it is unclear how autophagy is regulated after ultraviolet exposure in epidermal keratinocytes. Here, we found that the mRNAs of some key ATG genes such as ULK1, ATG5 and ATG7 exhibited significantly lower levels in the skin tissues of the face and chest with solar ultraviolet exposure, compared with perineal skin. Interestingly, UVB radiation down-regulated the expression of ULK1, ATG3 and ATG7, and it inhibited the autophagy flux via a mechanistic target of rapamycin (MTOR)-independent pathway in human keratinocytes. The inhibition of autophagy in UVB-treated keratinocytes cannot be restored by treatment with the MTOR-dependent autophagy inducer rapamycin. Importantly, UVB treatment perturbs the conversion of microtubule-associated protein 1 light chain 3 (LC3)-I to LC3-II and LC3-II turnover in response to treatment with MTOR inhibitors (Torin 1 and pp242), as well as endoplasmic reticular stress (A23187 and tunicamycin), inositol pathway (L690,330) and autophagy inducers (resveratrol and STF62247). Our study demonstrates that UVB radiation down-regulates several key autophagy-related proteins and impairs the autophagy response in keratinocytes. This study demonstrates a linkage between autophagy and skin disorders associated with ultraviolet exposure.
自噬是一种有助于维持细胞稳态的自我消化途径，许多自噬相关基因（ATG）参与自噬过程的调控。紫外线是皮肤常见的应激源，但目前尚不清楚紫外线照射后表皮角质形成细胞中的自噬是如何被调控的。在这里，我们发现，与会阴皮肤相比，面部和胸部皮肤组织在受到太阳紫外线照射后，一些关键ATG基因如ULK1、ATG5和ATG7的mRNA水平显著降低。有趣的是，UVB辐射下调了ULK1、ATG3和ATG7的表达，并通过一种不依赖雷帕霉素作用靶点（MTOR）的途径抑制了人角质形成细胞中的自噬通量。用依赖MTOR的自噬诱导剂雷帕霉素处理并不能恢复UVB处理的角质形成细胞中自噬的抑制。重要的是，UVB处理干扰了微管相关蛋白1轻链3（LC3）-I向LC3-II的转化以及LC3-II的周转，这是对MTOR抑制剂（托林1和pp242）、内质网应激（A23187和衣霉素）、肌醇途径（L690,330）和自噬诱导剂（白藜芦醇和STF62,247）处理的反应。我们的研究表明，UVB辐射下调了几种关键的自噬相关蛋白，并损害了角质形成细胞中的自噬反应。这项研究证明了自噬与紫外线暴露相关的皮肤疾病之间的联系。
