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Cavin-1 promotes M2 macrophages/microglia polarization via SOCS3

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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.

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Acknowledgements

Chinese government provided financial support in the form of the National Natural Science Foundation of China (No. 82060179, 82070982, 82000925 and 82101096), Natural Science Foundation of Guangxi Zhuang Autonomous Region (No. 2018GXNSFAA281128, No. 2018GXNSFBA281066, 2020GXNSFBA159015, 2018GXNSFAA050003, 2020GXNSFBA159057, No. 2018GXNSFBA050057 and 2021GXNSFBA075051) and Guangxi Science Base and Talents Special Program (GUIKE AD20297030).

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Author notes

  1. Wei Huang, Yiyi Hong and Wenjing He contributed equally to this work.

Authors and Affiliations

  1. Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology & Research Center of Ophthalmology, Guangxi Academy of Medical Sciences & Department of Ophthalmology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China

    Wei Huang, Yiyi Hong, Wenjing He, Li Jiang, Wen Deng, Biyan Peng, Fen Tang, Chaolan Shen, Qianqian Lan, Hui Huang, Haibin Zhong, Jian Lv, Siming Zeng, Min Li, Qi Chen, Ling Cui, Mingyuan Zhang, Fan Xu & Zhou Zhou

  2. Laboratory Animal Center, Guangxi Medical University, Nanning, 530021, China

    Yiqiang OuYang, Jinning Liang & Zhongxiang Mo

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  1. Wei Huang
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  2. Yiyi Hong
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Contributions

LJ, ZZ and FX: conceived and designed the experiments. JLv, WD and BP: performed cell culture and transfection work. WH, YH and CS: performed the western blotting analysis. qPCR was performed by BP, FT and HH, and Co-IP was performed by YOY, JL and ZM. WH, YH and FT: analyzed and interpreted the data. WH, LJ and YH: edited the paper. ML, QC, HZ, SZ, LC, FX and MZ: read and approved the final manuscript. WH is responsible for the revisions of the paper.

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Correspondence to Fan Xu or Zhou Zhou.

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Huang, W., Hong, Y., He, W. et al. Cavin-1 promotes M2 macrophages/microglia polarization via SOCS3. Inflamm. Res. 71, 397–407 (2022). https://doi.org/10.1007/s00011-022-01550-w

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