巨噬细胞移动抑制因子在创伤后关节挛缩后激活关节囊成纤维细胞的炎症反应。
Macrophage migration inhibitory factor activates the inflammatory response in joint capsule fibroblasts following post-traumatic joint contracture.
机构信息
Department of Rehabilitation Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Shanghai Key Laboratory of Orthopedic Implants, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
出版信息
Aging (Albany NY). 2021 Feb 17;13(4):5804-5823. doi: 10.18632/aging.202505.
OBJECTIVES
Joint capsule fibrosis caused by excessive inflammation leading to post-traumatic joint contracture (PTJC). Fibroblasts trigger inflammation under the challenge of various proinflammatory cytokines. Macrophage migration inhibitory factor (MIF) is a prominent proinflammatory cytokine involved in inflammation- and fibrosis-associated pathophysiology, we investigated the role of MIF in PTJC.
METHODS
Using rat PTJC model and fibroblast inflammation model, we detected MIF expression in posterior joint capsule. Primary joint capsule fibroblasts (JFs) were used to investigate the effects of MIF on cell proliferation, migration and proinflammatory cytokines production. The mechanism of JF-mediated events was evaluated by qRT-PCR, western blot and immunoprecipitation. We screened the mRNA expression profile to identify gene candidates that mediate the effect of MIF on JFs.
RESULTS
MIF increased in posterior joint capsule following PTJC and co-localized with fibroblasts. Injection of MIF inhibitor significantly suppressed joint capsule inflammation and fibrosis. , MIF promoted JF proliferation, migration, and inflammation by regulating mitogen-activated protein kinase/nuclear factor-κB pathway through coupling with CD74. Transcriptome analysis revealed that lipid metabolism-related factors Pla2g2a, Angptl4, and Sgpp2, downstream of MIF/CD74, were potentially implicated in JF inflammation.
CONCLUSION
MIF/CD74 axis elicited JF inflammation and may provide new therapeutic targets for joint capsule fibrosis in PTJC.
目的
由过度炎症引起的关节囊纤维化导致创伤后关节挛缩（PTJC）。成纤维细胞在各种促炎细胞因子的挑战下引发炎症。巨噬细胞移动抑制因子（MIF）是一种重要的促炎细胞因子，参与炎症和纤维化相关的病理生理学过程，我们研究了 MIF 在 PTJC 中的作用。
方法
使用大鼠 PTJC 模型和成纤维细胞炎症模型，检测后关节囊内 MIF 的表达。使用原代关节囊成纤维细胞（JFs）研究 MIF 对细胞增殖、迁移和促炎细胞因子产生的影响。通过 qRT-PCR、western blot 和免疫沉淀评估 JF 介导事件的机制。我们筛选了 mRNA 表达谱，以鉴定介导 MIF 对 JF 作用的基因候选物。
结果
PTJC 后后关节囊中 MIF 增加，并与成纤维细胞共定位。MIF 抑制剂的注射显著抑制了关节囊炎症和纤维化。此外，MIF 通过与 CD74 结合调节丝裂原活化蛋白激酶/核因子-κB 通路，促进 JF 增殖、迁移和炎症。转录组分析显示，MIF/CD74 下游的脂质代谢相关因子 Pla2g2a、Angptl4 和 Sgpp2 可能与 JF 炎症有关。
结论
MIF/CD74 轴引发 JF 炎症，可能为 PTJC 中的关节囊纤维化提供新的治疗靶点。
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