Cavin-1 promotes M2 macrophages/microglia polarization via SOCS3

Inflamm Res. 2022 Apr;71(4):397-407. doi: 10.1007/s00011-022-01550-w. Epub 2022 Mar 11.

Abstract

Purpose: Our study aimed to investigate the function of Cavin-1 and SOCS3 in macrophages/microglia M2 polarization and further explored the relevant mechanism.

Methods: Expression levels of Cavin-1 and SOCS3 in macrophages/microglia were measured by western blotting and RT-PCR, respectively. Then, Cavin-1 or SOCS3 was gene silenced by a siRNA approach, and gene silencing efficiency was determined by western blotting. Next, co-immunoprecipitation (Co-IP) was employed to further analyze the interaction between Cavin-1 and SOCS3. Finally, the activation of STAT6/PPAR-γ signaling was evaluated using western blotting, and the M2 macrophages/microglia polarization was validated by measuring the mRNA expression of M2 markers by RT-PCR.

Results: In the polarization process of macrophages/microglia to M2 phenotype, both Cavin-1 and SOCS3 increased synchronously at protein and mRNA level, reached the peak at the 6 h, and then decreased. After Cavin-1 or SOCS3 silencing, the expression of Cavin-1 and SOCS3 declined. These results suggested that Cavin-1 and SOCS3 were positively correlated in macrophages/microglia, and this conjecture was verified by Co-IP. Besides, Cavin-1 silencing not only suppressed the activation of STAT6/PPAR-γ pathway, but also suppressed the release of anti-inflammatory factors. Finally, we found that SOCS3 overexpression reversed the inhibitory effect of Cavin-1 silencing on the release of anti-inflammatory factors in M2 macrophages/microglia.

Conclusions: Cavin-1 and SOCS3 are actively involved in the process of M2 macrophages/microglia polarization. As a SOCS3 interacting protein, Cavin-1 can promote M2 macrophages/microglia polarization via SOCS3.

Keywords: Cavin-1; M2 Polarization; Macrophages; Microglia; SOCS3.

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Macrophages
  • Microglia* / metabolism
  • Peroxisome Proliferator-Activated Receptors* / metabolism
  • RNA, Messenger / metabolism

Substances

  • Anti-Inflammatory Agents
  • Peroxisome Proliferator-Activated Receptors
  • RNA, Messenger