Qinghai Provincial People's Hospital, Xining, Qinghai, P.R. China.
Department of Dermatology, The First People's Hospital of Xuzhou, Xuzhou, Jiangsu 221002, P.R. China.
Biosci Rep. 2021 Jul 30;41(7). doi: 10.1042/BSR20210609.
Alopecia areata is an autoimmune hair loss disease with infiltration of pro-inflammatory cells into hair follicles. The role of Tgr5 in dermatitis has attracted considerable attention. The present study aimed to investigate the effect of Tgr5 in the development of Alopecia areata.
The study utilized a comparison control group design with four groups of wild-type group, wild-type+INT777 group, Tgr5-/- group, and Tgr5-/-+INT777 group. The mice were treated with INT777 (30 mg/kg/day) or the carrier solution (DMSO) intraperitoneally for 7 weeks, and the back skin was collected and analyzed by histology and immunohistochemistry staining. The lumbar vertebrae 4 has also been analyzed by DXA and Micro-CT.
Tgr5-/- mice displayed the decreasingly significant in hair area and length, skin thickness, and the ratio of anagen and telogen, collagen, and mast cell number and loss the bone mass than WT group. After treating with INT777, the appearance of alopecia areata and bone microstructure has improved. Immunohistochemistry and qPCR analysis showed that activation of Tgr5 can down-regulate the express of JAK1, STAT3, IL-6, TNF-α, and VEGF.
These findings indicate that activation of Tgr5 mediated amelioration of alopecia areata and osteoporosis by down-regulated JAK1-STAT3 signaling pathway.
斑秃是一种自身免疫性脱发疾病，炎症细胞浸润毛囊。Tgr5 在皮炎中的作用引起了广泛关注。本研究旨在探讨 Tgr5 在斑秃发病机制中的作用。
采用野生型组、野生型+INT777 组、Tgr5-/-组和 Tgr5-/-+INT777 组的比较对照组设计。小鼠腹腔内分别给予 INT777（30mg/kg/天）或载体溶液（DMSO）7 周，采集背部皮肤进行组织学和免疫组化染色分析。还通过 DXA 和 Micro-CT 分析第 4 腰椎。
与 WT 组相比，Tgr5-/-小鼠的毛发面积和长度、皮肤厚度、生长期和退行期比例、胶原和肥大细胞数量以及骨量减少更为明显。用 INT777 处理后，斑秃和骨微结构的外观得到改善。免疫组化和 qPCR 分析表明，Tgr5 的激活可以下调 JAK1、STAT3、IL-6、TNF-α和 VEGF 的表达。
这些发现表明，Tgr5 的激活通过下调 JAK1-STAT3 信号通路改善斑秃和骨质疏松症。
