Department of Cardiovascular Medicine, Shaanxi Provincial People's Hospital, No.256 Youyi West Road, Beilin District, Xi'an City, 710068, Shaanxi Province, China.
J Transl Med. 2024 Jul 14;22(1):654. doi: 10.1186/s12967-024-05425-y.
Specific alterations in gut microbiota and metabolites have been linked to AMI, with CBLB potentially playing an essential role. However, the precise interactions remain understudied, creating a significant gap in our understanding. This study aims to address this by exploring these interactions in CBLB-intervened AMI mice using transcriptome sequencing, 16 S rDNA, and non-targeted metabolite analysis.
To probe the therapeutic potential and mechanistic underpinnings of CBLB overexpression in AMI, we utilized an integrative multi-omics strategy encompassing transcriptomics, metabolomics, and 16s rDNA sequencing. We selected these particular methods as they facilitate a holistic comprehension of the intricate interplay between the host and its microbiota, and the potential effects on the host's metabolic and gene expression profiles. The uniqueness of our investigation stems from utilizing a multi-omics approach to illuminate the role of CBLB in AMI, an approach yet unreported to the best of our knowledge. Our experimental protocol encompassed transfection of CBLB lentivirus-packaged vectors into 293T cells, followed by subsequent intervention in AMI mice. Subsequently, we conducted pathological staining, fecal 16s rDNA sequencing, and serum non-targeted metabolome sequencing. We applied differential expression analysis to discern differentially expressed genes (DEGs), differential metabolites, and differential microbiota. We performed protein-protein interaction analysis to identify core genes, and conducted correlation studies to clarify the relationships amongst these core genes, paramount metabolites, and key microbiota.
Following the intervention of CBLB in AMI, we observed a significant decrease in inflammatory cell infiltration and collagen fiber formation in the infarcted region of mice hearts. We identified key changes in microbiota, metabolites, and DEGs that were associated with this intervention. The findings revealed that CBLB has a significant correlation with DEGs, differential metabolites and microbiota, respectively. This suggests it could play a pivotal role in the regulation of AMI.
This study confirmed the potential of differentially expressed genes, metabolites, and microbiota in AMI regulation post-CBLB intervention. Our findings lay groundwork for future exploration of CBLB's role in AMI, suggesting potential therapeutic applications and novel research directions in AMI treatment strategies.
肠道微生物群和代谢物的特定改变与 AMI 有关，CBLB 可能发挥着重要作用。然而，这些确切的相互作用仍未得到充分研究，这在我们的理解中造成了一个重大的空白。本研究旨在通过使用转录组测序、16S rDNA 和非靶向代谢物分析来探索 CBLB 干预 AMI 小鼠中的这些相互作用来解决这个问题。
为了探究 CBLB 过表达在 AMI 中的治疗潜力和机制基础，我们利用了包含转录组学、代谢组学和 16S rDNA 测序的综合多组学策略。我们选择这些特定的方法是因为它们有助于全面理解宿主与其微生物群之间的复杂相互作用，以及它们对宿主代谢和基因表达谱的潜在影响。我们研究的独特之处在于利用多组学方法来阐明 CBLB 在 AMI 中的作用，据我们所知，这是一种尚未报道的方法。我们的实验方案包括将 CBLB 慢病毒包装载体转染到 293T 细胞中，然后对 AMI 小鼠进行后续干预。随后，我们进行了病理染色、粪便 16S rDNA 测序和血清非靶向代谢组学测序。我们应用差异表达分析来识别差异表达基因（DEGs）、差异代谢物和差异微生物群。我们进行了蛋白质-蛋白质相互作用分析以识别核心基因，并进行了相关性研究以阐明这些核心基因、主要代谢物和关键微生物群之间的关系。
在 CBLB 干预 AMI 后，我们观察到小鼠心脏梗死区域的炎症细胞浸润和胶原纤维形成明显减少。我们确定了与这种干预相关的关键微生物群、代谢物和 DEG 变化。研究结果表明，CBLB 与 DEGs、差异代谢物和微生物群分别具有显著相关性。这表明它可能在调节 AMI 中发挥关键作用。
本研究证实了 CBLB 干预后 AMI 调节中差异表达基因、代谢物和微生物群的潜力。我们的研究结果为未来探索 CBLB 在 AMI 中的作用奠定了基础，为 AMI 治疗策略中的潜在治疗应用和新的研究方向提供了依据。
