Advances in Research on Protein Arginine Methyltransferase 2: Functions
and Diseases

Min, Zhen-Qi; Jiang, Ming-Jun; Liu, Xi-Lian; Yuan, Su-Peng; Chen, Ping-An; Wang, Chu-Hao; Chen, Ya-Jun; Dai, Xian-Peng

doi:10.2174/0109298665281395231211060535

Cited by 1 publication

(1 citation statement)

References 149 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A previous study shed light on the significant associations between We found that C15orf39 produced biological effects, especially in terms of maintaining the microglial steady state via an interaction with PRMT2. PRMT2 is located on human chromosome 21 q22.3 [22,23]. According to the NCBI database, PRMT2 and C15orf39 are widely expressed in many organs, including the brain.…”

Section: Discussionmentioning

confidence: 99%

Human C15orf39 Inhibits Inflammatory Response via PRMT2 in Human Microglial HMC3 Cell Line

Zhang,

Xu,

Zhu

et al. 2024

IJMS

View full text Add to dashboard Cite

Microglia-mediated inflammatory response is one key cause of many central nervous system diseases, like Alzheimer’s disease. We hypothesized that a novel C15orf39 (MAPK1 substrate) plays a critical role in the microglial inflammatory response. To confirm this hypothesis, we used lipopolysaccharide (LPS) - and interferon-gamma (IFN-γ)-induced human microglia HMC3 cells as a representative indicator of the microglial in vitro inflammatory response. We found that C15orf39 was down-regulated when interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα) expression increased in LPS/IFN-γ-stimulated HMC3 cells. Once C15orf39 was overexpressed, IL-6 and TNFα expression were reduced in LPS/IFN-γ-stimulated HMC3 cells. In contrast, C15orf39 knockdown promoted IL-6 and TNFα expression in LPS/IFN-γ-stimulated HMC3 cells. These results suggest that C15orf39 is a suppressive factor in the microglial inflammatory response. Mechanistically, C15orf39 interacts with the cytoplasmic protein arginine methyltransferase 2 (PRMT2). Thus, we termed C15orf39 a PRMT2 interaction protein (PRMT2 IP). Furthermore, the interaction of C15orf39 and PRMT2 suppressed the activation of NF-κB signaling via the PRMT2-IkBα signaling axis, which then led to a reduction in transcription of the inflammatory factors IL6 and TNF-α. Under inflammatory conditions, NF-κBp65 was found to be activated and to suppress C15orf39 promoter activation, after which it canceled the suppressive effect of the C15orf39-PRMT2-IkBα signaling axis on IL-6 and TNFα transcriptional expression. In conclusion, our findings demonstrate that in a steady condition, the interaction of C15orf39 and PRMT2 stabilizes IkBα to inhibit IL-6 and TNFα expression by suppressing NF-κB signaling, which reversely suppresses C15orf39 transcription to enhance IL-6 and TNFα expression in the microglial inflammatory condition. Our study provides a clue as to the role of C15orf39 in microglia-mediated inflammation, suggesting the potential therapeutic efficacy of C15orf39 in some central nervous system diseases.

show abstract

Section: Discussionmentioning

confidence: 99%