2. Academic Validation
  3. PTGS2: A potential immune regulator and therapeutic target for chronic spontaneous urticaria

PTGS2: A potential immune regulator and therapeutic target for chronic spontaneous urticaria

  • Life Sci. 2024 Mar 19:122582. doi: 10.1016/j.lfs.2024.122582.
Yihui Chen 1,  Xingxing Jian 2,  Lei Zhu 1,  Pian Yu 1,  Xiaoqing Yi 1,  Qiaozhi Cao 1,  Jiayi Wang 1,  Feng Xiong 1,  Jie Li 3
Affiliations

Affiliations

  • 1 Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China; Furong Laboratory, Changsha 410008, China.
  • 2 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China; Bioinformatics Center, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China.
  • 3 Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China; Furong Laboratory, Changsha 410008, China. Electronic address: [email protected].
PMID: 38514006 DOI: 10.1016/j.lfs.2024.122582
Abstract

Aims: Chronic spontaneous urticaria (CSU) is a common and debilitating skin disease that is difficult to control with existing treatments, and the pathogenesis of CSU has not been fully revealed. The aim of this study was to explore the underlying mechanisms of CSU and identify potential treatments.

Materials and methods: Microarray datasets of CSU were obtained from Gene Expression Omnibus database. Differentially expressed genes between skin lesions of CSU and normal controls (LNS-DEGs) were identified, and the enrichment analyses of LNS-DEGs were performed. Hub genes of LNS-DEGs were selected by protein-protein interaction analysis. The co-expression and transcriptional regulatory networks of hub genes were conducted using GeneMANIA and TRRUST database, respectively. CIBERSORT was utilized for immune cell infiltration analysis. Experimental validation was performed by β-hexosaminidase release examination and passive cutaneous anaphylaxis (PCA) mouse model.

Key findings: A total of 247 LNS-DEGs were identified, which were enriched in cell migration, cell chemotaxis, and inflammatory pathways such as TNF and interleukin (IL) -17 signaling pathway. Among LNS-DEGs, seven upregulated (PTGS2, CCL2, IL1B, CXCL1, IL6, VCAM1, ICAM1) and one downregulated hub gene (PECAM1) were selected. Immune infiltration analysis identified eight different immune cells, such as activated/resting mast cells and neutrophils. Furthermore, PTGS2, encoding cyclooxygenase 2 (COX2), was selected for further validation. COX2 inhibitor, celecoxib, significantly inhibited mast cell degranulation, and reduced vascular permeability and inflammatory cytokine expression in PCA mouse model.

Significance: PTGS2 may be a potential regulator of immunity and inflammation in CSU. Targeting PTGS2 is a new perspective for CSU treatment.

Keywords

Bioinformatics; Chronic spontaneous urticaria; Immune; Inflammation; PTGS2.

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