P38 and JNK signal pathways are involved in the regulation of phlorizin against UVB-induced skin damage
P38 and JNK signal pathways are involved in the regulation of phlorizin against UVB-induced skin damage
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P38 和 JNK 信号通路参与根皮苷对 UVB 引起的皮肤损伤的调节
DOI：
10.1111/exd.12642
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发表时间：
2015-04-01
影响因子：
3.6
通讯作者：
Ye, Xiyun
中科院分区：
文献类型：
--
作者：
Zhai, Yimiao;Dang, Yongyan;Ye, Xiyun
众所周知，根茎苷能抑制肾脏和肠道中的钠/葡萄糖共转运体，用于治疗糖尿病、肥胖症和应激性高血糖。然而，根茎苷抗中波紫外线(UVB)辐射的作用及其分子机制尚不清楚。通过体外和体内实验，观察根茎苷对UVB照射后皮肤角质形成细胞凋亡、活性氧(ROS)产生、促炎反应及某些信号分子变化的影响。我们观察到根茎苷预处理抑制了UVB诱导的HaCaT细胞的凋亡和ROS的过量产生。根茎皂苷还能在基因水平上降低UVB诱导的促炎细胞因子IL-1β、IL-6和IL-8的表达。裸鼠UVB照射后局部涂抹根茎苷可防止皮肤鳞片和红斑的形成，抑制表皮增厚，减轻皮肤急性炎症渗出。此外，通过聚合酶链式反应、免疫印迹和免疫组织化学检测结果表明，根茎苷在体外和体内均能逆转UVB辐射诱导的环氧合酶-2(COX-2)的过表达。中波紫外线照射后p38和JNK丝裂原活化蛋白激酶(MAPK)的激活也被根茎苷抑制。这些结果提示根茎皂苷通过减少ROS的过度产生、COX-2的表达以及随后的过度炎症反应来有效地保护皮肤免受UVB诱导的皮肤损伤。似乎p38和JNK MAPK信号通路参与了根茎皂苷保护功能的调节。
Phlorizin is well known to inhibit sodium/glucose cotransporters in the kidney and intestine for the treatment of diabetes, obesity and stress hyperglycaemia. However, the effects of phlorizin against ultraviolet B (UVB) irradiation and its molecular mechanism are still unknown. We examined the effects of phlorizin on skin keratinocyte apoptosis, reactive oxygen species (ROS) production, pro-inflammatory responses after UVB irradiation and the changes of some signal molecules by in vitro and in vivo assay. We observed that phlorizin pretreatments inhibited HaCaT cell apoptosis and overproduction of ROS induced by UVB. Phlorizin also decreased the expression of UVB-induced pro-inflammatory cytokines, such as interleukin-1 beta (IL-1), interleukin-6 (IL-6) and interleukin-8 (IL-8) at the mRNA level. Topical application of phlorizin on UVB-exposed skin of nude mice prevented the formation of scaly skin and erythema, inhibited the increase of epidermal thickness and reduced acute inflammation infiltration in skin. Additionally, PCR, Western blot and immunohistochemical data showed that phlorizin reversed the overexpression of cyclooxygenase-2 (Cox-2) induced by UVB irradiation both in vitro and in vivo. The activation of p38 and JNK mitogen-activated protein kinases (MAPK) after UVB irradiation was also inhibited by phlorizin. These findings suggest that phlorizin is effective in protecting skin against UVB-induced skin damage by decreasing ROS overproduction, Cox-2 expression and the subsequent excessive inflammation reactions. It seemed that p38 and JNK MAPK signal pathways are involved in the regulation of the protective function of phlorizin.