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PPAR-γ promotes the polarization of rat retinal microglia to M2 phenotype by regulating the expression of CD200-CD200R1 under hypoxia

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Abstract

Background

Recent reports suggest that peroxisome proliferator-activated receptor-γ (PPAR-γ) could promote microglial M2 polarization to inhibit inflammation. However, the specific molecular mechanisms that trigger PPAR-γ’s anti-inflammatory ability in microglia are yet to be expounded. Thus, in this study, we aimed to explore the molecular mechanisms behind the anti-inflammatory effects of PPAR-γ in hypoxia-stimulated rat retinal microglial cells.

Methods and results

We used shRNA expressing lentivirus to knock down PPAR-γ and CD200 genes, and we assessed hypoxia-induced polarization markers release – M1 (iNOS, IL-1β, IL-6, and TNF-α) and M2 (Arg-1, YM1, IL-4, and IL-10) by RT-PCR. We also monitored PPAR-γ-related signals (PPAR-γ, PPAR-γ in cytoplasm or nucleus, CD200, and CD200Rs) by Western blot and RT-PCR. Our results showed that hypoxia enhanced PPAR-γ and CD200 expressions in microglial cells. Moreover, PPAR-γ agonist 15d-PGJ2 elevated CD200 and CD200R1 expressions, whereas sh-PPAR-γ had the opposite effect. Following hypoxia, expressions of M1 markers increased significantly, while those of M2 markers decreased, and the above effects were attenuated by 15d-PGJ2. Conversely, knocking down PPAR-γ or CD200 inhibited the polarization of microglial cells to M2 phenotype.

Conclusion

Our findings demonstrated that PPAR-γ performed an anti-inflammatory function in hypoxia-stimulated microglial cells by promoting their polarization to M2 phenotype via the CD200-CD200R1 pathway.

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Funding

This work was supported by the Natural Science Foundation of Guangxi Zhuang Autonomous Region (No. 2018GXNSFAA281128), the National Natural Science Foundation of China (No. 82060179, No. 82070982) and Guangxi Clinical Ophthalmic Research Center (No. AD19245193).

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Author notes

  1. Yiyi Hong and Li Jiang contributed equally to this work. Changzheng Chen and Lifei Chen are co-corresponding authors.

Authors and Affiliations

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

    Hong Yiyi, Jiang Li, Tang Fen, Cui Ling, Zhong Haibin, Xu Fan, Li Min & Chen Lifei

  2. Eye Center, Renmin Hospital of Wuhan University, Wuhan, 430060, China

    Hong Yiyi & Chen Changzheng

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

    Zhang Mingyuan

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  1. Hong Yiyi
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Yiyi Hong and Li Jiang. The first draft of the manuscript was written by Yiyi Hong and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Chen Changzheng or Chen Lifei.

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Hong, Y., Jiang, L., Tang, F. et al. PPAR-γ promotes the polarization of rat retinal microglia to M2 phenotype by regulating the expression of CD200-CD200R1 under hypoxia. Mol Biol Rep 50, 10277–10285 (2023). https://doi.org/10.1007/s11033-023-08815-5

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