Journal of Molecular Histology

, Volume 50, Issue 4, pp 355–367 | Cite as

MIF/CD74 axis participates in inflammatory activation of Schwann cells following sciatic nerve injury

  • Honghua Song
  • Ziwen Zhu
  • Yue Zhou
  • Nan Du
  • Tiancheng Song
  • Hao Liang
  • Xiaojun Chen
  • Yingjie Wang
  • Yongjun Wang
  • Yuming HuEmail author
Original Paper


Based on deep RNA sequencing of distal segments of lesioned sciatic nerves, a huge number of differentially expression genes (DEGs) were thus obtained and functionally analyzed. The inflammatory response was denoted as one of most significant biological processes following sciatic nerve injury. In the present study, ingenuity pathway analysis (IPA) demonstrated that macrophage migration inhibitory factor (MIF) was identified as a core regulator of inflammatory response through interaction with CD74 membrane receptor. By establishment of rat sciatic nerve transection model, we displayed that MIF was upregulated following sciatic nerve axotomy, in colocalization with Schwann cells (SCs). MIF promoted migration, proliferation, together with inflammatory responses of SCs in vitro. Immunoprecipitation showed that MIF interacted with CD74 receptor, through which to activate intracellular ERK and JNK signaling pathways. Interference of CD74 receptor using specific siRNA showed that the transcription of proinflammatory cytokines including TNF-α, IL-1β, as well as cytokine receptor TLR4 in SCs was significantly attenuated, supporting an participation of MIF/CD74 signal axis in SCs inflammatory response. The data provide a novel role of MIF in eliciting inflammatory response of peripheral nerve injury, which might be beneficial for precise therapy of peripheral nerve inflammation.


Peripheral nerve injury RNA sequencing Ingenuity pathway analysis Inflammatory response MIF Schwann cells 



This study was supported by the Basic Scientific Research Projects of Nantong (JC2018065).

Compliance with ethical standards

Ethical approval

Animal experiments were performed in strict accordance with the Institutional Animal Care guidelines.

Supplementary material

10735_2019_9832_MOESM1_ESM.xlsx (30.3 mb)
Supplementary material 1 (XLSX 30,996 kb)


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Honghua Song
    • 1
  • Ziwen Zhu
    • 2
  • Yue Zhou
    • 3
  • Nan Du
    • 2
  • Tiancheng Song
    • 2
  • Hao Liang
    • 2
  • Xiaojun Chen
    • 2
  • Yingjie Wang
    • 2
  • Yongjun Wang
    • 2
  • Yuming Hu
    • 3
    Email author
  1. 1.Department of PediatricsAffiliated Hospital of Nantong UniversityNantongPeople’s Republic of China
  2. 2.Key Laboratory of Neuroregeneration of Jiangsu and Ministry of EducationNantong UniversityNantongPeople’s Republic of China
  3. 3.Department of Rehabilitation MedicineAffiliated Hospital of Nantong UniversityNantongPeople’s Republic of China

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