Macrophage migration inhibitory factor regulates joint capsule fibrosis by promoting TGF-P1 production in fibroblasts

Joint capsule fibrosis caused by excessive inflammation results in post-traumatic joint contracture (PTJC). Transforming growth factor (TGF)-P1 plays a key role in PTJC by regulating fibroblast functions, however, cytokine-induced TGF-P1 expression in specific cell types remains poorly characterized. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in inflammation- and fibrosis-associated pathophysiology. In this study, we investigated whether MIF can facilitate TGF-P1 production from fibroblasts and regulate joint capsule fibrosis following PTJC. Our data demonstrated that MIF and TGF-P1 significantly increased in fibroblasts of injured rat posterior joint capsules. Treatment the lesion sites with MIF inhibitor 4-Iodo-6-phenylpyrimidine (4-IPP) reduced TGF-P1 production and relieved joint capsule inflammation and fibrosis. In vitro, MIF facilitated TGF-P1 expression in primary joint capsule fibroblasts by activating mitogen-activated protein kinase (MAPK) (P38, ERK) signaling through coupling with membrane surface receptor CD74, which in turn affected fibroblast functions and promoted MIF production. Our results reveal a novel function of trauma-induced MIF in the occurrence and development of joint capsule fibrosis. Further investigation of the underlying mechanism may provide potential therapeutic targets for PTJC.

Automated summary

This study revealed the role of MIF and TGF-β1 in post-traumatic joint contracture, showing that MIF can enhance TGF-β1 production in fibroblasts through MAPK signaling, leading to fibroblast function changes and joint capsule fibrosis. Further investigation into this mechanism may lead to potential therapeutic targets for PTJC.