Aberrant amino acid metabolism promotes neurovascular reactivity in rosacea.
Aberrant amino acid metabolism promotes neurovascular reactivity in rosacea.
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异常的氨基酸代谢促进红斑痤疮的神经血管反应性
DOI：
10.1172/jci.insight.161870
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发表时间：
2022-11-22
期刊：
影响因子：
8
通讯作者：
Li, Ji
中科院分区：
文献类型：
--
作者：
Liu, Tangxiele;Xiao, Wenqin;Chen, Mengting;Mao, Rui;Xu, San;Peng, Qinqin;Zhao, Zhixiang;Wang, Qian;Xie, Hongfu;Deng, Zhili;Li, Ji
酒渣鼻是一种慢性皮肤病，其特征是面部中央神经血管异常和炎症。尽管越来越多的证据表明酒渣鼻与代谢紊乱有关，但代谢在酒渣鼻发病机制中的作用仍不清楚。在这里，通过靶向代谢组学方法，我们表征了酒渣鼻患者显著改变的代谢特征，特别是氨基酸相关的代谢途径。其中，谷氨酸和天冬氨酸与酒渣鼻患者疾病严重程度显著正相关。我们进一步证明，谷氨酸和天冬氨酸可以促进小鼠皮肤红斑和毛细血管扩张的发展，这是酒渣鼻的典型特征。从机制上讲，谷氨酸和天冬氨酸刺激了周围神经元和角质形成细胞血管舒张相关神经肽的产生，并诱导内皮细胞和角质形成细胞释放一氧化氮。有趣的是，我们提供的证据表明，多西环素可能通过靶向氨基酸代谢途径改善酒渣鼻患者的症状。这些发现表明，氨基酸代谢异常促进了酒糟鼻的神经血管反应性，并提出了靶向代谢失调作为临床治疗的一种有希望的策略的可能性。
Rosacea is a chronic skin disorder characterized by abnormal neurovascular and inflammatory conditions on the central face. Despite increasing evidence suggesting that rosacea is associated with metabolic disorders, the role of metabolism in rosacea pathogenesis remains unknown. Here, via a targeted metabolomics approach, we characterized significantly altered metabolic signatures in patients with rosacea, especially for amino acid-related metabolic pathways. Among these, glutamic acid and aspartic acid were highlighted and positively correlated with the disease severity in patients with rosacea. We further demonstrated that glutamic acid and aspartic acid can facilitate the development of erythema and telangiectasia, typical features of rosacea, in the skin of mice. Mechanistically, glutamic acid and aspartic acid stimulated the production of vasodilation-related neuropeptides from peripheral neurons and keratinocytes and induced the release of nitric oxide from endothelial cells and keratinocytes. Interestingly, we provided evidence showing that doxycycline can improve the symptoms of patients with rosacea possibly by targeting the amino acid metabolic pathway. These findings reveal that abnormal amino acid metabolism promotes neurovascular reactivity in rosacea and raise the possibility of targeting dysregulated metabolism as a promising strategy for clinical treatment.
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影响因子：
6.6
作者：
Ferreira Mello, Bruna Stefania;Maia Chaves Filho, Adriano Jose;Macedo, Danielle S.
通讯作者：
Macedo, Danielle S.
影响因子：
2.7
作者：
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通讯作者：
Feng, Hao
中国长沙市红斑痤疮流行病学特征：基于人群的横断面研究
影响因子：
3.1
作者：
Li Jinglin;Wang Ben;Xie Hongfu
通讯作者：
Xie Hongfu
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影响因子：
13.8
作者：
Chen, Qi;Shi, Xiao;Li, Ji
通讯作者：
Li, Ji
影响因子：
3.8
作者：
Bostanci, N.;Akguel, B.;McKay, I. J.
通讯作者：
McKay, I. J.