作者: Hou, Yunqing ; Duan, Xiaoru ; Liu, Xinxin ; Chai, Bao ; Lin, Shiying ; Liu, Xin ; Kong, Yi ; Li, Man ; Li, Li ; Luo, Qingtian ; Chen, Hongxiang ; Zhang, Yinlian ; Zhang, Jingyu ; Yu, Mingyu ; Liu, Suwen ; Jiang, Jian ; Tao, Qingxiao ; Zhang, Song

Neuroimmunological mechanisms are essential for maintaining bodily homeostasis. Abnormal activation of these mechanisms is significantly linked to various skin disorders and constitutes a significant component in the development of these diseases. However, the involvement of neuroimmunological interactions in psoriasis pathogenesis is not yet fully understood. In this study, we identify the peripheral nervous system as a significant source of interleukin-6 (IL-6), which contributes to skin inflammation and acts as a key regulator in the onset and progression of psoriasis. Through single-cell sequencing analysis of mouse dorsal root ganglia (DRG) tissue, we identified a specific group of neurons that secrete IL-6. These neurons exhibited elevated levels of IL-6 expression following treatment with imiquimod (IMQ). Additionally, we observed a reciprocal regulatory relationship between the peripheral nervous system and immune cells. Neuronal activity is tightly controlled by surrounding macrophages. The expression of IL-6 is regulated by the secreted IL-1β upon M1 polarization, and dependent on MAPK signaling. Consequently, IL-6 is secreted from neurons into the skin, exacerbating the development and progression of psoriasis. This study reveals the mechanisms by which sensory neurons regulate psoriasis through IL-6, further clarifying the neuropsychiatric factors involved in the pathogenesis of psoriasis. It offers new insights for the clinical treatment of psoriasis.

2025-08-01·MOLECULES AND CELLS

Iron Metabolism Dysregulation and Ferroptosis: Emerging Drivers in Pulmonary Fibrosis Pathogenesis and Therapy

Review

作者: Zhu, Xiangxing ; Lin, Yuandong ; Tang, Dongsheng ; Chen, Yingshan ; Jiang, Yawen ; Wang, Tao ; Zhu, Zhu ; Zhang, Ligang

Ferroptosis is an iron-dependent and regulated form of cell death, characterized by lipid peroxidation and oxidative stress. The progressive development of pulmonary fibrosis (PF) is closely linked to the ferroptosis pathway. Although the underlying mechanisms remain incompletely defined, this field has drawn intense research attention. Notable progress has been made in identifying ferroptosis-related metabolic pathways and key targets during PF development. In this review, we first summarize the basic regulation of iron metabolism in the human lung, iron metabolic imbalance, and the activation of ferroptosis. Second, we focus on elaborating the mechanistic connections between ferroptosis and PF, encompassing the clinical features, pathological manifestations, and core pathogenic mechanisms of PF, as well as the interplay between ferroptosis and three specific cell types in PF: alveolar epithelial cells, macrophages, and fibroblasts. Thirdly, the research progress in the pharmacotherapy of PF is categorized into three categories: drugs already approved for PF and those under clinical trials; ferroptosis-targeted therapeutic strategies, including inhibitors, natural compounds, gene therapy, and combination strategies. This review, grounded in key metabolic pathways and therapeutic targets, systematically explores the complex relationships among iron metabolic disorders, ferroptosis, and PF progression. Our aim is to provide a theoretical and practical foundation for ferroptosis-targeted PF treatment.

2025-05-01·Science China-Life Sciences

Inhibition of KDM6B prevents osteoarthritis by blocking growth plate-like H3K27me3 loss in bivalent genes

Article

作者: You, Xuanhe ; Xiao, Ke ; Lu, Hanpeng ; Du, Hao ; Luo, Zhenyu ; Liao, Zhixin ; Zeng, Jiancheng ; Du, Ze ; Yang, Fan ; Wu, Diwei ; Zhou, Zongke ; Huang, Shishu ; Ning, Ning ; Cai, Yongrui ; Shi, Peiliang ; Gan, Fangji ; Zhang, Yao ; Ding, Bi-Sen ; Zhao, Ya ; Yu, Xi ; Wang, Yan

Osteoarthritis (OA) is the most prevalent joint disorder occurring with articular cartilage degradation. It includes a switch from an articular to a growth plate chondrocyte phenotype. Here, we investigated the histone modification profiles and found significant H3K27me3 loss in OA, which led to disease-associated gene expression. Surprisingly, these genes were occupied by both H3K27me3 and H3K4me3 in normal chondrocytes, showing a poised bivalent state. Furthermore, we observed the derepression of similar bivalent genes in growth plate chondrocytes. Finally, a KDM6B inhibitor GSK-J4 prevented the H3K27me3 loss and cartilage damage in the rat OA model. Our results reveal an inherited bivalent epigenetic signature on developmental genes that makes articular chondrocytes prone to hypertrophy and contributes to a promising epigenetic therapy for OA.

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项与江苏集萃药康生物科技股份有限公司相关的新闻（医药）

2025-08-29

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