胆酸通过 G 蛋白偶联胆汁酸受体 1 促进酒渣鼻样皮肤炎症。
Lithocholic acid promotes rosacea-like skin inflammation via G protein-coupled bile acid receptor 1.
机构信息
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China; Hunan key laboratory of aging biology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, China; Center for Obesity and Metabolic Disease Research, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
出版信息
Biochim Biophys Acta Mol Basis Dis. 2022 Dec 1;1868(12):166563. doi: 10.1016/j.bbadis.2022.166563. Epub 2022 Sep 27.
BACKGROUND
Rosacea is a chronic inflammatory skin disorder with unclear etiology. Evidence showed that immunoinflammatory dysregulation was involved in the pathogenesis. Bile acids, as important participants of hepatoenteric circulation, play a vital role in immunoinflammatory regulation through peripheral blood circulation. However, whether it has effects on rosacea remains unknown.
METHODS
Here, we performed a bile acid analysis on the serum samples of rosacea patients and healthy controls. Then we gavage G protein-coupled bile acid receptor 1 (TGR5) knockout mice with lithocholic acid (LCA) based on a LL37-induced rosacea-like model. We further overexpress TGR5 in HaCaT keratinocytes to figure out the downstream pathway.
RESULTS
We found varied bile acid profile in the peripheral blood circulation of patients, especially the most significant increase in LCA. LCA promoted skin inflammation in LL37-induced rosacea-like mouse model. Our in vivo and in vitro results further demonstrated that LCA induced inflammatory cytokines and chemokines, thus exacerbated rosacea-like skin inflammation, via TGR5 in keratinocytes and LL37-induced rosacea-like mouse model.
CONCLUSIONS
Therefore, we conclude that LCA promotes skin inflammation of rosacea via TGR5, and LCA-TGR5 axis may be a novel therapeutic target for rosacea.
背景
酒渣鼻是一种病因不明的慢性炎症性皮肤疾病。有证据表明，免疫炎症失调参与了其发病机制。胆酸作为肝胆循环的重要参与者，通过外周血液循环在免疫炎症调节中发挥着重要作用。然而，其是否对酒渣鼻有影响尚不清楚。
方法
我们对酒渣鼻患者和健康对照者的血清样本进行了胆酸分析。然后，我们基于 LL37 诱导的酒渣鼻样模型，用石胆酸（LCA）对 G 蛋白偶联胆酸受体 1（TGR5）敲除小鼠进行灌胃。我们进一步在 HaCaT 角质形成细胞中过表达 TGR5，以确定下游途径。
结果
我们在患者的外周血液循环中发现了不同的胆酸谱，尤其是 LCA 的显著增加。LCA 在 LL37 诱导的酒渣鼻样小鼠模型中促进了皮肤炎症。我们的体内和体外结果进一步表明，LCA 通过角质形成细胞中的 TGR5 和 LL37 诱导的酒渣鼻样小鼠模型，诱导炎症细胞因子和趋化因子，从而加剧酒渣鼻样皮肤炎症。
结论
因此，我们得出结论，LCA 通过 TGR5 促进酒渣鼻的皮肤炎症，LCA-TGR5 轴可能是酒渣鼻的一个新的治疗靶点。
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