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To investigate the role of RAS-like activator 2 (RASAL2) in metabolic dysfunction-associated steatohepatitis (MASH) and its underlying mechanism.
A murine MASH model was established by feeding a high-fat diet for 24 weeks. Hepatic inflammatory gene expression levels were quantified by qRT-PCR. Hepatic immune cell infiltration was assessed by flow cytometry. Bone marrowderived macrophages (BMDMs) were isolated and cultured in vitro, followed by stimulation with lipopolysaccharide to induce M1 polarization. The expression levels of M1 polarization markers (Nos2, Il1b, Il6, Tnf, Arg1, CD206, Il10) were measured by qRT-PCR. The protein expressions of p-IκBα, IκBα, p-IKKβ, IKKβ, p-P65, and P65 were determined by Western blot.
Compared with wild-type littermates, RASAL2-knockout mice exhibited markedly decreased hepatic inflammatory cell infiltration, reduced hepatic mRNA levels of Il1b, Il6, and Tnf, and increased Il10 expression. Flow cytometry revealed a reduction in hepatic immune cells infiltration and a decrease in M1 macrophages in RASAL2-knockout mice. In vitro experiments showed that RASAL2 knockout reduced the expression of M1 polarization marker genes (Nos2, Il1b, Il6, Tnf), increased the expression of M2 polarization marker genes (Arg1, CD206, Il10), and inhibited the activation of NF-κB pathway.
RASAL2 knockout attenuates hepatic inflammatory injury in MASH and inhibits M1 macrophage polarization. Its mechanism may be related to the suppression of the NF-κB signaling pathway.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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