Mycoplasma pneumoniae (MP) can infect both the upper and lower respiratory tracts. Polydatin (PD), a traditional Chinese medicine, is known to have anti-inflammation and antifibrosis properties. However, the protective effects of PD against MP pneumonia (MPP) remain unclear. So, the aim of this study was to describe the therapeutic effects and underlying mechanisms of PD against MPP. BALB/c mice were assigned to three groups: a normal control group, MP infection group, or PD-treated MP infection group. BEAS-2B cells transfected with or without NACHT domain-, leucine-rich repeat-, and pyd-containing protein 3 (NLRP3) were used to confirm the protective mechanisms of PD. Immunohistochemical analysis, Western blot analysis, enzyme-linked immunosorbent assay, and flow cytometry were used in this study. The results showed that PD treatment suppressed MP-induced lung injury in mice by suppressing the expression of inflammatory factors and inhibiting the development of pulmonary fibrosis. Meanwhile, PD treatment inhibited activation of the NLRP3 inflammasome and nuclear factor κB (NF-κB) pathway. Overexpression of NLRP3 reversed the protective effect of PD against MPinduced injury of BEAS-2B cells. Taken together, these results indicate that PD treatment suppressed the inflammatory response and the development of pulmonary fibrosis by inhibiting the NLRP3 inflammasome and NF-κB pathway after MP infection. K E Y W O R D S fibrosis, inflammation, Mycoplasma pneumoniae, NACHT domain-, leucine-rich repeat-, and pyd-containing protein 3, polydatin
Background As the most prevalent chemical modifications on eukaryotic mRNAs, N6-methyladenosine (m6A) methylation was reported to participate in the regulation of various metabolic diseases. This study aimed to investigate the roles of m6A methylation and methyltransferase-like16 (METTL16) in non-alcoholic fatty liver disease (NAFLD). Methods In this study, we used a model of diet-induced NAFLD, maintaining six male C57BL/6J mice on high-fat diet (HFD) to generate hepatic steatosis. The high-throughput sequencing and RNA sequencing were performed to identify the m6A methylation patterns and differentially expressed mRNAs in HFD mice livers. Furthermore, we detected the expression levels of m6A modify enzymes by qRT-PCR in liver tissues, and further investigated the potential role of METTL16 in NAFLD through constructing overexpression and a knockdown model of METTL16 in HepG2 cells. Results In total, we confirmed 15,999 m6A recurrent peaks in HFD mice and 12,322 in the control. Genes with differentially methylated m6A peaks were significantly associated with the dysregulated glucolipid metabolism and aggravated hepatic inflammatory response. In addition, we identified five genes (CIDEA, THRSP, OSBPL3, GDF15 and LGALS1) that played important roles in NAFLD progression after analyzing the differentially expressed genes containing differentially methylated m6A peaks. Intriguingly, we found that the expression levels of METTL16 were substantially increased in the NAFLD model in vivo and in vitro, and further confirmed that METTL16 upregulated the expression level of lipogenic genes CIDEA in HepG2 cells. Conclusions These results indicate the critical roles of m6A methylation and METTL16 in HFD-induced mice and cell NAFLD models, which broaden people’s perspectives on potential m6A-related treatments and biomarkers for NAFLD.
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