IMMUNOLOGY LETTERS
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2025
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IF 2.8
Yu Zhang,Nannan Tong,Siyu Hao,He Ma,Yuzhen Li
Psoriasis is a systemic inflammatory disorder that has a significant impact on the quality of life of patients. E74-like factor 3 (ELF3) is a common transcriptional mediator of inflammation, but the effect of ELF3 on psoriasis development and severity is poorly understood. In this study, we first collected clinical normal skin tissues and skin tissues of psoriasis patients to detect the mRNA and protein levels of ELF3 and found that ELF3 was highly expressed in psoriasis skin tissues. We further used the imiquimod (IMQ)-induced mice model to mimic the phenotypic changes of human psoriasis in vivo , which are manifested as scaling, epidermal hyperplasia, and erythema formation, but knockdown of ELF3 resulted in suppression of these phenomena. In addition, downregulation of ELF3 expression inhibited neoangiogenesis and inflammatory cell infiltration. On this basis, we further found that ELF3 promotes the proliferation, angiogenesis, and inflammatory response of human keratinocyte HaCaT in vitro . Mechanistically, we found that ELF3 transcriptionally activated the activity of the downstream factor ADAM metallopeptidase domain 8 (ADAM8) by dual luciferase assays, thereby exacerbating the severity of psoriasis. We concluded that ELF3 is a key target for exacerbating psoriasis pathologic manifestations and promoting disease progression.
研究领域:
免疫学
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皮肤病学
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分子生物学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
FASEB JOURNAL
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2025
·Vol. 39
·期 22
·e71217
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IF 4.2
Ji Li,Wenwen Zhang,Yue Zhang,Huanqiu Liu
Hepatic ischemia–reperfusion injury (HIRI) is a local aseptic inflammatory response driven by innate immunity, and it can severely damage liver function. ADAM8 belongs to the ADAM (a disintegrin and metalloprotease domain) family and has been shown to be important in inflammation-related diseases. However, its role in HIRI remains unknown. ADAM8 expression was increased in the liver tissues of HIRI mice, which was also correlated with the progression of liver damage. Suppression of ADAM8 alleviated I/R-induced liver damage in mice, ameliorating hepatocyte injury and the release of inflammatory cytokines. ADAM8 knockdown upregulated the expression of CD31 and downregulated CD45 in liver tissues. In addition, ADAM8 knockdown downregulated Ly6G and citH3 double-positive cells in the liver tissue of HIRI mice, reducing the protein expression of citH3, indicating ADAM8 knockdown relieved neutrophil infiltration and the formation of neutrophil extracellular traps during HIRI. In OGD/R-treated C166 cells, ADAM8 was upregulated. ADAM8 knockdown inhibited endothelial cell permeability and neutrophil transmigration. Moreover, catalytic residue mutation of ADAM8 did not affect its protein expression but impaired the promotion of ADAM8 on endothelial cell permeability and neutrophil transmigration. BK-1361, an inhibitor of ADAM8, also attenuated endothelial cell permeability and neutrophil transmigration. Animal experiments confirmed that BK-1361 alleviates HIRI. These results suggested that the function of ADAM8 in disrupting the endothelial cell barrier and exacerbating leukocyte extravasation is dependent on its enzymatic activity. In summary, ADAM8 aggravates HIRI by disrupting the endothelial barrier, increasing endothelial permeability, accelerating leukocyte extravasation, and promoting the inflammatory response and hepatocyte injury. Graphical Hepatic ischemia–reperfusion injury (HIRI) is a local aseptic inflammatory response driven by innate immunity, and it can severely damage liver function. In this work, we found that ADAM8 expression was increased in the liver tissues of HIRI mice, which was also correlated with the progression of liver damage. Suppression of ADAM8 abated HIRI development by disrupting the endothelial barrier, increasing endothelial permeability, accelerating leukocyte extravasation, and the inflammatory response.
研究领域:
免疫学
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肝脏病学
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炎症
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分子生物学
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血管生物学
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产品关联
DOI
PubMed
高影响因子
AMERICAN JOURNAL OF SPORTS MEDICINE
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2025
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IF 4.5
Baoyun Xu,Yunjiao Wang,Gang He,Xu Tao,Shang Gao,Mei Zhou,Yuzhen Tang,Kang-lai Tang,Lin Guo,Wan Chen
Background:The challenge of achieving effective tendon-to-bone healing remains a significant concern in sports medicine, necessitating further exploration. Biomimetic electrospun nanomaterials present promising avenues for improving this critical healing process.Purpose:To investigate the biological efficacy of a novel aligned-to-random PLGA/Col1-PLGA/nHA bilayer electrospun nanofiber membrane in facilitating tendon-to-bone healing.Study Design:Controlled laboratory study.Methods:The bilayer membrane’s composition, combining PLGA/Col1 for tendon attachment and PLGA/nHA for bone integration, was examined using scanning electron microscopy, Fourier transform infrared spectroscopy, and mechanical testing. Positioned between the Achilles tendon and bone, its design aimed for harmonious integration with both types of tissue. In vitro, biocompatibility, cell adhesion, and proliferation of the biomaterial were evaluated using live/dead staining and the CCK-8 assay. Collagen secretion and mineralization were measured for 2 cell types. In vivo, tendon-to-bone insertion samples harvested from mice were analyzed: micro–computed tomography assessed bone formation; histological staining evaluated chondrogenesis, tendinogenesis, and the 4-layer structure of the insertion; and biomechanical testing measured insertion strength. Real-time polymerase chain reaction identified genes involved in tendon-to-bone healing, and transcriptome analysis elucidated the underlying cellular and molecular mechanisms.Results:The optimal composition was determined as 10% 3:1 for aligned PLGA/Col1 and 9% 5:1 for PLGA/nHA. Coculture showed minimal cell death, firm cell adherence, and steady proliferation, with PLGA/Col1 enhancing collagen secretion. In vivo, the material promoted bone and cartilage formation and improved tendon-to-bone interface strength. Transcriptome analysis indicated links to TNF and NF-κB pathways and to genes IL-1β, ADAM8, and EGR2.Conclusion:The novel aligned-to-random PLGA/Col1-PLGA/nHA bilayer nanofiber membrane outperformed other materials in both in vitro and in vivo evaluations, significantly enhancing tendon-to-bone healing. It notably improved cartilage and bone formation, tendon maturation, and biomechanical strength at the surgical interface. These effects may be associated with the TNF and NF-κB pathways and with the genes IL-1β, ADAM8, and EGR2.Clinical Relevance:This study introduces a biomimetic nanofiber membrane enhancing tendon-to-bone healing, which is crucial for sports medicine. Its efficacy in improving healing outcomes, including bone and cartilage formation and biomechanical strength, could significantly lower failure rates in surgical procedures such as rotator cuff repair and anterior cruciate ligament reconstruction. This advancement offers promising implications for patient recovery and the effectiveness of surgical interventions in tendon-to-bone injuries.
研究领域:
运动医学
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组织工程
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生物材料科学
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骨科
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生物医学工程
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DOI
PubMed
高影响因子
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