eNeuro
·
2024
·
IF 2.7
Yonghong Tan,Qiong Wang,Yubing Guo,Na Zhang,Yingyi Xu,Xue Bai,Jianhua Liu,Xiaobao Bi
Pyroptosis, an inflammatory Programmed cell death, has recently been found to play an important role in spinal cord injury (SCI). C-type lectin domain family 5 member A (CLEC5A), triggering receptor expressed on myeloid cells 1 (TREM1), and NLR-family CARD-containing protein 4 (NLRC4) have been reported to be associated with neuronal pyroptosis, but few studies have clarified their functions and regulatory mechanisms in SCI. In this study, CLEC5A, TREM1, and NLRC4 were highly expressed in lidocaine-induced SCI rat models, and their knockdown alleviated lidocaine-induced SCI. The elevation of proptosis related indicators LDH, ASC, GSDMD-N, IL-18, caspase-1, and IL-1β levels in SCI rats was attenuated after silencing of CLEC5A, TREM1, or NLRC4. Lidocaine-induced the decrease in cell viability and the elevation in cell death were partly reversed after CLEC5A, TREM1, or NLRC4 silencing. Lidocaine-mediated effects on the levels of LDH, ASC, GSDMD-N, IL-18, caspase-1, and IL-1β in lidocaine-induced PC-12 cells were weakened by downregulating CLEC5A, TREM1, or NLRC4. CLEC5A could interact with TREM1 to mediate NLRC4 expression, thus accelerating neuronal pyroptosis, ultimately leading to SCI exacerbation. In conclusions, CLEC5A interacted with TREM1 to increase NLRC4 expression, thus promoting neuronal pyroptosis in rat SCI models, providing new insights into the role of neuronal pyroptosis in SCI.Significance statement Pyroptosis has been reported to be involved in SCI. Higher levels of CLEC5A, TREM1, and NLRC4 associated with neuronal pyroptosis. However, the role and regulatory mechanism of CLEC5A, TREM1, and NLRC4 in SCI were not clear. Here, high expression of CLEC5A, TREM1, and NLRC4 was observed in lidocaine-induced SCI rat models. CLEC5A could interact with TREM1 to enhance the expression of NLRC4, thus accelerating neuronal pyroptosis in rat SCI models. These findings identify CLEC5A, TREM1, and NLRC4 as potential therapeutic targets for SCI.
研究领域:
神经科学
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细胞生物学
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炎症
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脊髓损伤
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产品关联
DOI
PubMed
高影响因子
Bioengineered
·
2022
·
IF 6.832
Miao Zhang,Chengkun Yin,Yan Chen,Juan Wang,Jing Jiang
Triggering receptor expressed on myeloid cells 1 (TREM1) participates in the development of endometritis. This study aims at identifying the effects and interaction of TREM1 and upstream stimulatory factor 2 (USF2) in endometritis by using a model of lipopolysaccharide (LPS)-induced human endometrial epithelial cells (HEnEpCs). ELISA was performed to determine the levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF-α) after LPS stimulation. TREM1 and USF2 expression was examined with RT-qPCR and Western blot. The JASPAR database was employed to predict the binding site between USF2 and TREM1, which was confirmed by luciferase reporter and chromatin immunoprecipitation assays. After TREM1 overexpression, IL-6, IL-1β, and TNF-α expression was detected by ELISA. Next, the binding of TREM1 to toll-like receptor (TLR) 2/4 was examined with co-immunoprecipitation. Then, proteins in TLR2/4-nuclear factor-kappaB (NF-κB) signaling in HEnEpCs under LPS condition were assessed by Western blot or immunofluorescence before and after TREM1 knockdown. Finally, TLR2 or TLR4 was silenced to explore whether intervene TLR2/4-NF-κB signaling pathway could rescue TREM1-overexpression-induced inflammation in LPS-induced HEnEpCs. Results revealed that upregulated TREM1 was observed in LPS-challenged HEnEpCs. Next, USF2 was found to have transcriptionally active TREM1 expression. Additionally, USF2 knockdown decreased the levels of IL-6, IL-1β, and TNF-α, whereas this effect was rescued after TREM1 overexpression. Besides, TREM1 could bind to TLR2/4 to regulate NF-κB signaling. Moreover, the intervention of TLR2/4-NF-κB signaling pathway rescued TREM1-overexpression-induced inflammation in LPS-stimulated HEnEpCs. Collectively, USF2 promotes endometritis by upregulating TREM1, thereby activating TLR2/4-NF-κB pathway.
研究领域:
免疫学
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细胞生物学
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分子生物学
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妇科学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR MEDICINE
·
2024
·Vol. 30
·期 1
·1-16
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IF 6
Zhang Yanbin,Bai Jing,Xiao Bin,Li Chunyan
Osteoporosis is characterized by reduced bone mass due to imbalanced bone metabolism. Exosomes derived from bone mesenchymal stem cells (BMSCs) have been shown to play roles in various diseases. This study aimed to clarify the regulatory function and molecular mechanism of BMSCs-derived exosomes in osteogenic differentiation and their potential therapeutic effects on osteoporosis. Exosomes were extracted from BMSCs. Bone marrow-derived macrophages (BMDMs) were cultured and internalized with BMSCs-derived exosomes. Real-time quantitative PCR was used to detect the expression of macrophage surface markers and tripartite motif (TRIM) family genes. BMDMs were co-cultured with human osteoblasts to assess osteogenic differentiation. Western blot was performed to analyze the ubiquitination of triggering receptor expressed on myeloid cell 1 (TREM1) mediated by TRIM25. An ovariectomized mice model was established to evaluate the role of TRIM25 and exosomes in osteoporosis. Exosomes were successfully isolated from BMSCs. BMSCs-derived exosomes upregulated TRIM25 expression, promoting M2 macrophage polarization and osteogenic differentiation. TRIM25 facilitated the ubiquitination and degradation of TREM1. Overexpression of TREM1 reversed the enhanced M2 macrophage polarization and osteogenic differentiation caused by TRIM25 overexpression. TRIM25 enhanced the protective effect of BMSCs-derived exosomes against bone loss in mice. These findings suggested that BMSCs-derived exosomes promoted osteogenic differentiation by regulating M2 macrophage polarization through TRIM25-mediated ubiquitination and degradation of TREM1. This mechanism might provide a novel approach for treating osteoporosis.
研究领域:
细胞生物学
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骨代谢
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干细胞研究
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巨噬细胞生物学
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疾病分子机制
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产品关联
DOI
PubMed
高影响因子
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