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