Regulatory Effects of IL-36γ on the Function of Human Skin Fibroblasts through JAK-STAT Signaling Pathway

GE Jingyao¹, WU Chenchen², ZHANG Kaoyuan², HU Hao¹, LIU Xiaojuan¹, WU Jiali², LI Manhui¹, DOU Xia^2*, CHEN Xiaofan^1*

(¹Shenzhen Key Laboratory for Translational Medicine of Dermatology, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China; ²Department of Dermatology, Peking University Shenzhen Hospital, Shenzhen 518036, China)

Abstract:

This study investigates the effects of IL-36γ (interleukin-36γ) on the activation of human dermal fibroblasts and its influence on the JAK-STAT signaling pathway. After human primary dermal fibroblasts were treated with IL-36γ, cell proliferation and migration were assessed using the CCK-8 assay and scratch wound heal ing assay, respectively. The expression of fibrosis-related genes, including COL1A1, COL3A1, COL5A1, α-SMA, CCN2, and LUM, were quantified by qRT-PCR. GO (Gene Ontology) functional analysis, KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis, and GSEA (Gene Set Enrichment Analysis) were employed to identify potential regulatory pathways that mediated the effects of IL-36γ on the activation of human dermal fibroblasts. Western blot analysis was used to detect the expression and activation of JAK3 and STAT3, key proteins in the JAK-STAT pathway. The effects of IL-36γ on skin fibroblasts were investigated following the inhibi tion of STAT3 phosphorylation with a selective inhibitor. The results demonstrated that IL-36γ not only enhanced the proliferation and migration of dermal fibroblasts but also upregulated the expression of fibrosis-associated genes involved in extracellular matrix deposition. GO functional analysis revealed that the effects of IL-36γ were associ ated with extracellular matrix structural components and collagen binding. KEGG pathway enrichment analysis and GSEA further indicated activation of the JAK-STAT pathway in response to IL-36γ. Experimental validation confirmed that activation of the JAK-STAT signaling pathway is critical for regulating fibrosis-related gene expres sion. These findings suggest that IL-36γ effectively promotes the proliferation, migration, and activation of dermal f ibroblasts through the activation of the JAK-STAT signaling pathway.

CSTR: 32200.14.cjcb.2025.06.0008