Effects of MOGAT1 and Androgen Receptor on the Pathogenesis of Acne in Mice
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摘要:
目的 探讨单酰基甘油 O-酰基转移酶 1（monoacylglycerol O-acyltransferase 1，MOGAT1）抑制痤疮发生发展的作用机制。 方法 通过皮下注射痤疮丙酸杆菌P. acnes建立小鼠痤疮模型。利用亚油酸（linoleic acid，LA）处理SZ95细胞构建痤疮体外模型。通过RT-qPCR 检测相关因子的mRNA水平，Western blot检测相关蛋白表达，相应试剂盒检测活性氧（reactive oxygen species，ROS）水平、过氧化氢酶（catalase，CAT）含量和超氧化物歧化酶（superoxide dismutase，SOD）活性，ELISA试剂盒检测各组细胞和组织中白细胞介素-6（interleukin-6，IL-6）、白细胞介素-1β（interleukin-1 beta，IL-1β）和肿瘤坏死因子α（tumor necrosis factor-alpha，TNF-α）水平，油红O染色检测细胞中脂质积累，HE染色检测小鼠皮肤组织的病变。 结果 与正常组比较，模型组小鼠皮肤组织和细胞中MOGAT1 mRNA和蛋白表达显著升高（P < 0.001）。敲低MOGAT1可缓解模型组小鼠的皮肤损伤、抑制炎症因子的表达、敲低 MOGAT1 的治疗效果接近阳性药物。敲低MOGAT1增强SOD（P < 0.0001 ）和CAT（P <0.0001 ）活性，降低甘油三酯含量（P <0.0001 ），此外，MOGAT1敲低能特异性抑制AR/SREBP-1通路和脂质代谢。结论 敲低MOGAT1 通过靶向调控 AR/SREBP-1 信号轴，有效抑制脂质异常积累及炎症反应，从而在痤疮发生发展中发挥保护作用。 Abstract:Objective To explore the mechanism by which monoacylglycerol O-acyltransferase 1 （MOGAT1） inhibits the occurrence and development of acne. Methods An acne mouse model was established by subcutaneous injection of Propionibacterium acnes （P. acnes）. An in vitro acne model was constructed by treating SZ95 cells with linoleic acid （LA）. RT-qPCR was used to detect mRNA levels of relevant factors, Western blot was used to detect protein expression, corresponding kits were used to detect reactive oxygen species （ROS） levels, catalase （CAT） content, and superoxide dismutase （SOD） activity. ELISA kits were used to detect interleukin-6 （IL-6）, interleukin-1 beta （IL-1β）, and tumor necrosis factor-alpha （TNF-α） levels in cells and tissues of each group. Oil Red O staining was used to detect lipid accumulation in cells, and hematoxylin and eosin （HE） staining was used to detect pathological changes in mouse skin tissue. Results Compared with the normal group, MOGAT1 mRNA and protein expression were significantly increased in skin tissue and cells of the model group mice （P < 0.001）. Knockdown of MOGAT1 alleviated the skin damage of the model mice, inhibited inflammatory factor expression, and the therapeutic effect of MOGAT1 knockdown was comparable to that of positive drug control. Knockdown of MOGAT1 enhanced the activity of SOD （P < 0.0001 ） and CAT （P <0.0001 ）, reduced triglyceride content （P <0.0001 ）, and in addition, MOGAT1 knockdown specifically inhibited the AR/SREBP-1 pathway and lipid metabolism.Conclusion MOGAT1 knockdown exerts a protective effect in the occurrence and development of acne by targeting and regulating the AR/SREBP-1 signaling axis, effectively inhibiting abnormal lipid accumulation and inflammatory responses. -
Key words:
- acne /
- MOGAT1 /
- inflammation /
- lipid metabolism /
- androgen receptor
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图 1 痤疮小鼠模型建立及相关检测 （$ \bar x \pm s $，n = 6）
A：PCR检测皮肤组织中MOGAT1的表达；B～C：Western blot检测皮肤组织中MOGAT1的表达；D～E：HE染色检测皮肤组织的损伤；F～K：ELISA检测血清中相关因子的表达；K～Q：PCR检测皮肤组织中脂质代谢相关因子的表达；**P < 0.01；***P < 0.001；****P < 0.0001。
Figure 1. Establishment of acne mouse model and related detection methods （$ \bar x \pm s $，n = 6）
图 2 敲低MOGAT1对痤疮小鼠的影响 （$ \bar x \pm s $，n = 6）
A：PCR检测MOGAT1的表达；B～C：HE染色检测皮肤组织的损伤；D～I：ELISA检测血清中相关因子的表达；J：Western blot检测皮肤组织中脂质代谢相关因子的表达；K～M：PCR检测SOD1、Fasn、ACACA的表达；*P < 0.05；**P < 0.01；***P < 0.001；****P < 0.0001；ns：差异无统计学意义。
Figure 2. Effects of MOGAT1 knockdown on acne mouse model （$ \bar x \pm s $，n = 6）
图 3 敲低MOGAT1对皮脂腺细胞的影响 （$ \bar x \pm s $，n = 3）
A：PCR检测MOGAT1的表达；B～C：Western blot检测MOGAT1蛋白的表达；D～F：ELISA检测细胞上清液中相关因子的表达；H～J：生化试剂盒检测细胞中氧化应激相关指标的表达；*P < 0.05；**P < 0.01；***P < 0.001；****P < 0.0001；ns：差异无统计学意义。
Figure 3. Effects of MOGAT1 knockdown on sebaceous gland cells （$ \bar x \pm s $，n = 3）
图 4 敲低MOGAT1对皮脂腺细胞脂质生成的影响 （$ \bar x \pm s $，n = 3）
A：生化试剂盒检测甘油三酯含量；B～E：PCR检测SOD1、PPARγ、Fasn、ACACA的表达；F～I：Western blot检测脂质代谢相关因子的蛋白表达；J～L：Western blot检测细胞核和胞浆中AR的蛋白表达；H：油红O染色检测细胞中的脂质积累。*P < 0.05；**P < 0.01；***P < 0.001；****P < 0.0001；ns：差异无统计学意义。
Figure 4. Effect of MOGAT1 knockdown on lipogenesis in sebocytes （$ \bar x \pm s $，n = 3）
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