中华皮肤科杂志 ›› 2024, Vol. 57 ›› Issue (4): 309-315.doi: 10.35541/cjd.20230091

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基于高通量测序对反常性痤疮中PPAR通路作用的初步探讨

何艳艳1，2    马骁1，2    惠云3    王雯竹1，2    王宝玺4    曾荣1，2，5    徐浩翔1，2   

  1. 1中国医学科学院  北京协和医学院皮肤病医院，南京  210042；2江苏省皮肤病与性病分子生物学重点实验室，南京  210042； 3解放军东部战区总医院皮肤科，南京  210002；4中国医学科学院  北京协和医学院整形外科医院，北京  100144；5云南中医药大学第一附属医院皮肤科，昆明  650021
  • 收稿日期:2023-02-21 修回日期:2024-01-08 发布日期:2024-04-07
  • 通讯作者: 曾荣；徐浩翔 E-mail:zengrong2010@hotmail.com; xbpipi@163.com
  • 基金资助:
    国家自然科学基金（81703148）；江苏省老年健康科研项目（LK2021024）；中国医学科学院医学与健康科技创新工程项目（CIFMS-2021-I2M-1-001）

Role of peroxisome proliferator-activated receptor signaling pathway in acne inversa by high-throughput sequencing: a preliminary study

He Yanyan1,2, Ma Xiao1,2, Hui Yun3, Wang Wenzhu1,2, Wang Baoxi4, Zeng Rong1,2,5, Xu Haoxiang1,2   

  1. 1Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China; 2Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing 210042, China; 3Department of Dermatology, General Hospital of Eastern Theater Command, Nanjing 210002, China; 4Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100144, China; 5Department of Dermatology, First Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming 650021, China
  • Received:2023-02-21 Revised:2024-01-08 Published:2024-04-07
  • Contact: Zeng Rong; Xu Haoxiang E-mail:zengrong2010@hotmail.com; xbpipi@163.com
  • Supported by:
    National Natural Science Foundation of China （81703148）; Research Program of Geriatric Health of Jiangsu Province （LK2021024）; CAMS Innovation Fund for Medical Sciences （CIFMS-2021-I2M-1-001）

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摘要： 【摘要】 目的 探讨过氧化物酶体增殖物激活受体（PPAR）信号通路在反常性痤疮发病机制中的功能。方法 于2013—2019年收集中国医学科学院皮肤病医院8例反常性痤疮皮损和4例健康对照组皮肤组织进行高通量测序，获得反常性痤疮皮损特异性表达谱，进行基因本体论（GO）分析，京都基因与基因组百科全书（KEGG）分析和基因集富集分析（GSEA）。实时荧光定量PCR（qPCR）和Western印迹法验证高通量测序结果。结果 特异性表达谱显示，与健康对照组相比，反常性痤疮皮损组共筛选出2 738条差异表达基因，其中1 328条基因显著上调，1 410条基因显著下调。GO分析显示，干扰素γ分泌的正向调控、T细胞受体复合体及C-X-C趋化因子受体活性等在反常性痤疮皮损中被显著富集；KEGG分析显示，原发性免疫缺陷、PPAR通路及趋化因子-趋化因子受体相互作用等通路在反常性痤疮皮损中被显著富集；GSEA显示，反常性痤疮皮损中PPAR信号通路被显著削弱。反常性痤疮皮损组PPARA、PPARG的转录水平（0.336 ± 0.120、0.253 ± 0.078）低于健康对照组（1.000 ± 0.146、1.000 ± 0.172，t = 3.50、3.95，均P < 0.05），其蛋白水平也显著低于健康对照组，而PPARD的转录水平与健康对照组差异无统计学意义（t = 0.34，P = 0.750）。反常性痤疮皮损组核激素受体9顺式维A酸受体α亚型（RXRA）、RXRG和脂肪酸结合蛋白4的转录水平均低于健康对照组（t = 2.96、2.96、4.62，P < 0.05）。结论 反常性痤疮患者中PPAR信号通路被抑制，脂质代谢途径发生紊乱。

关键词: 化脓性汗腺炎, 过氧化物酶体增殖物激活受体, 高通量核苷酸序列分析, PPARα, PPARγ, 脂肪代谢

Abstract: 【Abstract】 Objective To explore the role of peroxisome proliferator-activated receptor （PPAR） signaling pathway in the pathogenesis of acne inversa （AI）. Methods Skin tissue samples were obtained from 8 AI patients and 4 healthy controls from Hospital of Dermatology, Chinese Academy of Medical Science and Peking Union Medical College from 2013 to 2019, and high-throughput sequencing was performed for tissue-specific mRNA expression profiling. Gene Ontology （GO） analysis, Kyoto Encyclopedia of Genes and Genomes （KEGG） analysis, and Gene Set Enrichment Analysis （GSEA） were carried out. Real-time fluorescence-based quantitative PCR （qPCR） and Western blot analysis were performed to verify the results of high-throughput sequencing. Results Analysis of the specific expression profiles showed that 2 738 differentially expressed genes were screened out in the AI patients compared with the healthy controls, of which 1 328 genes were significantly up-regulated and 1 410 genes were significantly down-regulated. GO analysis demonstrated that the positive regulation of interferon γ secretion, T cell receptor complex and C-X-C chemokine receptor activity were significantly enriched in the AI lesions. KEGG analysis demonstrated that the signaling pathways associated with primary immuno‐deficiency, PPAR, and chemokine-chemokine receptor interaction were significantly enriched in the AI lesions. GSEA demonstrated that the PPAR signaling pathway was significantly weakened in the AI lesions. The mRNA expression levels of PPARA and PPARG were significantly lower in the AI patients （0.336 ± 0.120, 0.253 ± 0.078, respectively） than in the healthy group （1.000 ± 0.146, 1.000 ± 0.172, t = 3.50, 3.95, respectively, both P < 0.05）, so were their protein levels. However, there was no significant difference in the PPARD mRNA expression level between the two groups （t = 0.34, P = 0.750）. The mRNA expression levels of nuclear hormone receptor 9-cis retinoid X receptor alpha （RXRA）, RXRG and fatty acid-binding protein 4 were significantly lower in the AI patients than in the healthy controls （t = 2.96, 2.96, 4.62, respectively, all P < 0.05）. Conclusion The PPAR signaling pathway was restrained and lipid metabolism was disordered in AI patients.

Key words: Hidradenitis suppurativa, Peroxisome proliferator-activated receptors, High-throughput nucleotide sequencing, PPARα, PPARγ, Lipid metabolism

引用本文

何艳艳 马骁 惠云 王雯竹 王宝玺 曾荣 徐浩翔. 基于高通量测序对反常性痤疮中PPAR通路作用的初步探讨[J]. 中华皮肤科杂志, 2024,57(4):309-315. doi:10.35541/cjd.20230091

He Yanyan, Ma Xiao, Hui Yun, Wang Wenzhu, Wang Baoxi, Zeng Rong, Xu Haoxiang, . Role of peroxisome proliferator-activated receptor signaling pathway in acne inversa by high-throughput sequencing: a preliminary study[J]. Chinese Journal of Dermatology, 2024, 57(4): 309-315.doi:10.35541/cjd.20230091