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和在通过 RIG-I 受体信号通路抑制山羊肌肉脂肪细胞分化中的功能作用及其分子特征。

Molecular Characterizations of and Its Functional Role in Inhibiting the Differentiation of Goat Intramuscular Adipocytes through RIG-I Receptor Signaling Pathway.

机构信息

Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Ministry of Education, Southwest Minzu University, Chengdu 610041, China.

Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Exploitation of Sichuan Province, Southwest Minzu University, Chengdu 610041, China.

出版信息

Genes (Basel). 2024 Aug 30;15(9):1143. doi: 10.3390/genes15091143.

Abstract

The aim of this study was to elucidate the effect of on the differentiation of goat intramuscular precursor adipocytes and its mechanism of action. Here, we cloned the CDS region 2094 bp of the goat gene, encoding a total of 697 amino acid residues. Functionally, overexpression of inhibited the differentiation of goat intramuscular adipocytes with a concomitant reduction in lipid droplets, whereas interference with expression promoted the differentiation of goat intramuscular adipocytes. To further investigate the mechanism of inhibiting adipocyte differentiation, 104 differentially expressed genes were screened by RNA-seq, including 95 up-regulated genes and 9 down-regulated genes. KEGG analysis found that the RIG-I receptor signaling pathway, NOD receptor signaling pathway and toll-like receptor signaling pathway may affect adipogenesis. We selected the RIG-I receptor signaling pathway enriched with more differential genes as a potential adipocyte differentiation signaling pathway for verification. Convincingly, the RIG-I like receptor signaling pathway inhibitor (HY-P1934A) blocked this pathway to save the phenotype observed in intramuscular adipocyte with overexpression. Finally, the upstream miRNA of was predicted, and the targeted inhibition of miR-21-5p on the expression of gene was confirmed. In this study, it was found that FAM13A inhibited the differentiation of goat intramuscular adipocytes through the RIG-I receptor signaling pathway, and the upstream miRNA of (miR-21-5p) promoted the differentiation of goat intramuscular adipocytes. This work extends the genetic regulatory network of IMF deposits and provides theoretical support for improving human health and meat quality from the perspective of IMF deposits.

摘要

本研究旨在阐明 FAM13A 对山羊肌内前体脂肪细胞分化的影响及其作用机制。在此,我们克隆了山羊 FAM13A 基因的 CDS 区 2094 bp,共编码 697 个氨基酸残基。功能上,过表达 FAM13A 抑制了山羊肌内脂肪细胞的分化,伴随着脂滴减少,而干扰 FAM13A 表达则促进了山羊肌内脂肪细胞的分化。为了进一步研究 FAM13A 抑制脂肪细胞分化的机制,我们通过 RNA-seq 筛选出了 104 个差异表达基因,包括 95 个上调基因和 9 个下调基因。KEGG 分析发现,RIG-I 受体信号通路、NOD 受体信号通路和 Toll 样受体信号通路可能影响脂肪生成。我们选择富含更多差异基因的 RIG-I 样受体信号通路作为潜在的脂肪细胞分化信号通路进行验证。令人信服的是,RIG-I 样受体信号通路抑制剂(HY-P1934A)阻断了该通路,挽救了 FAM13A 过表达时观察到的肌内脂肪细胞表型。最后,预测了 FAM13A 的上游 miRNA,并证实了靶向抑制 miR-21-5p 对 FAM13A 基因表达的作用。本研究发现 FAM13A 通过 RIG-I 受体信号通路抑制山羊肌内脂肪细胞分化,而 FAM13A 的上游 miRNA(miR-21-5p)则促进山羊肌内脂肪细胞分化。这项工作扩展了 IMF 沉积的遗传调控网络,为从 IMF 沉积的角度提高人类健康和肉质提供了理论支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fdb/11430868/bdaa5d85ffe1/genes-15-01143-g001.jpg

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