Shikonin induces apoptosis and suppresses growth in keratinocytes via CEBP-delta upregulation
Shikonin induces apoptosis and suppresses growth in keratinocytes via CEBP-delta upregulation
复制标题
紫草素通过 CEBP-δ 上调诱导细胞凋亡并抑制角质形成细胞的生长
DOI：
10.1016/j.intimp.2019.04.047
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发表时间：
2019
影响因子：
5.6
通讯作者：
Geng Long
中科院分区：
文献类型：
--
作者：
Yu Ya jie;Xu Yuan yuan;Lan Xiao ou;Li Xiao ying;Zhang Xiao lan;Gao Xing hua;Geng Long
紫草素是东方药用植物Leptospermumerythrorhizon的活性化合物，其先前已显示抑制银屑病样炎症。然而，其潜在机制尚不清楚。本研究从体外和体内两个方面探讨了紫草素对银屑病角质形成细胞增殖和凋亡的影响机制。我们的研究结果表明，紫草素显着抑制细胞增殖，并通过靶向CEBPD诱导HaCaT和LV-STAT 3 HaCaT细胞凋亡，而细胞存活，增殖和活力的下降，通过流式细胞术和MTS检测发现。此外，紫草素灌胃明显减轻银屑病样表现在IMQ诱导的BALB/c小鼠临床（PASI评分）和组织病理学。免疫组织化学显示，紫草素有效地抑制JAK/STAT 3信号通路在局部皮肤病变和增加CEBPD表达。这些结果表明紫草素抑制角质形成细胞增殖并诱导凋亡，这导致通过JAK/STAT 3依赖性途径治疗银屑病。此外，JAK/STAT 3的激活下调HaCaT细胞和MQ诱导的BALB/c小鼠中的CEBPD。然而，紫草素可以逆转这些作用，表明CEBPD可能是银屑病的潜在治疗靶点。
Shikonin is an active compound of the oriental medicinal plant, Leptospermumerythrorhizon,which has been previously shown to inhibit psoriasis-like inflammation. However, the underlying mechanism is unclear. In the present study, the mechanisms of keratinocyte proliferation and apoptosis in psoriasis in response to shikonin were explored both in vitro and in vivo. Our results showed that shikonin significantly inhibits cell proliferation and induces apoptosis in both HaCaT and LV-STAT3 HaCaT cells by targeting CEBPD, while a decrease in cell survival, proliferation and viability were found through flow-cytometry and MTS assay. Furthermore, gavage with shikonin markedly alleviated psoriasis-like manifestations in IMQ-induced BALB/c mice clinically (PASI Score) and histopathologically. Immunohistochemistry revealed that shikonin potently suppresses the JAK/STAT3 signaling pathway in local skin lesions and increases CEBPD expression. These results imply that shikonin inhibits keratinocyte proliferation and induces apoptosis, which results in psoriasis treatment through the JAK/STAT3 dependent pathway. In addition, the activation of JAK/STAT3 downregulates CEBPD in HaCaT cells and IMQ-induced BALB/c mice. However, shikonin can reverse these effects, suggesting that CEBPD may be a potential therapeutic target for psoriasis.