The CEBPA-FGF21 regulatory network may participate in the T2DM-induced skeletal muscle atrophy by regulating the autophagy-lysosomal pathway

IF 3.1 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Acta Diabetologica Pub Date : 2023-07-01 DOI:10.1007/s00592-023-02131-x
Kai Wu, Sha Huang, Fan Zheng, Yuan Liu
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引用次数: 1

Abstract

Aims

Recent years have witnessed an increasing research interest in the roles of transcription factor (TF)-gene regulatory network in type 2 diabetes mellitus (T2DM). Thus, we sought to characterize the mechanistic insights based on the TF-gene regulatory network in skeletal muscle atrophy in T2DM.

Methods

Differentially expressed TFs (DETFs) and mRNAs (DEmRNAs) were obtained in T2DM-related gene expression profiles (GSE12643, GSE55650, GSE166502, and GSE29221), followed by WGCNA, and GO and KEGG enrichment analyses. Next, the iRegulon plug-in unit of Cytoscape software was used to construct a TF-mRNA regulatory network. Besides, RT-qPCR and ChIP-seq were utilized to measure the expression of CEBPA and FGF21 in the skeletal muscle tissues or cells of T2DM rat models. At last, the effect of overexpression of FGF21 on the autophagy-lysosomal pathway was examined in skeletal muscle cells of T2DM rats.

Results

Totally, 12 DETFs and 102 DEmRNAs were found in the skeletal muscle tissues of T2DM samples. The DEmRNAs were mainly enriched in the autophagy-lysosomal pathway. CEBPA affected the skeletal muscle atrophy in T2DM by regulating 5 target genes via the autophagy-lysosomal pathway. CEBPA could target FGF21. In addition, the expression of CEBPA was elevated, while the expression of FGF21 was diminished in the skeletal muscle tissues or cells of T2DM rats. The CEBPA-FGF21 regulatory network promoted skeletal muscle atrophy in T2DM by activating the autophagy-lysosomal pathway.

Conclusion

The CEBPA-FGF21 regulatory network may participate in the T2DM-induced skeletal muscle atrophy by regulating the autophagy-lysosomal pathway. Thus, our study provides interesting targets for prevention of skeletal muscle atrophy in T2DM.

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CEBPA-FGF21调控网络可能通过调节自噬-溶酶体途径参与T2DM诱导的骨骼肌萎缩
近年来,转录因子(TF)基因调控网络在2型糖尿病(T2DM)中的作用引起了越来越多的研究兴趣。因此,我们试图基于TF基因调控网络来表征T2DM骨骼肌萎缩的机制。方法在T2DM相关基因表达谱(GSE12643、GSE55650、GSE166502和GSE29221)中获得差异表达的TF(DETF)和mRNA(DEmRNA),然后进行WGCNA、GO和KEGG富集分析。接下来,使用Cytoscape软件的iRegulon插件单元构建TF mRNA调控网络。此外,利用RT-qPCR和ChIP-seq检测了CEBPA和FGF21在T2DM大鼠模型骨骼肌组织或细胞中的表达。最后,在T2DM大鼠骨骼肌细胞中检测了FGF21过表达对自噬溶酶体途径的影响。结果在T2DM患者骨骼肌组织中共发现12个DETF和102个DEmRNA。DEmRNA主要富集在自噬-溶酶体途径中。CEBPA通过自噬-溶酶体途径调节5个靶基因,从而影响T2DM患者的骨骼肌萎缩。CEBPA可以靶向FGF21。此外,在T2DM大鼠的骨骼肌组织或细胞中,CEBPA的表达升高,而FGF21的表达降低。CEBPA-FGF21调控网络通过激活自噬溶酶体途径促进T2DM患者的骨骼肌萎缩。结论CEBPA-FGF21调控网络可能通过调节自噬-溶酶体途径参与T2DM诱导的骨骼肌萎缩。因此,我们的研究为预防T2DM患者的骨骼肌萎缩提供了有趣的靶点。
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来源期刊
Acta Diabetologica
Acta Diabetologica 医学-内分泌学与代谢
CiteScore
7.30
自引率
2.60%
发文量
180
审稿时长
2 months
期刊介绍: Acta Diabetologica is a journal that publishes reports of experimental and clinical research on diabetes mellitus and related metabolic diseases. Original contributions on biochemical, physiological, pathophysiological and clinical aspects of research on diabetes and metabolic diseases are welcome. Reports are published in the form of original articles, short communications and letters to the editor. Invited reviews and editorials are also published. A Methodology forum, which publishes contributions on methodological aspects of diabetes in vivo and in vitro, is also available. The Editor-in-chief will be pleased to consider articles describing new techniques (e.g., new transplantation methods, metabolic models), of innovative importance in the field of diabetes/metabolism. Finally, workshop reports are also welcome in Acta Diabetologica.
期刊最新文献
Glial fibrillary acidic protein: a potential biomarker for small fiber neuropathy? Increasing HbA1c in children and youth with a first-degree relative with type 1 diabetes predicts progression to diabetes: a single-centre 10-year screening experience. Analysis of postprandial time trends and influencing factors of blood glucose and insulin in type 2 diabetes mellitus (T2DM) with metabolic dysfunction-associated steatotic liver disease (MASLD): a retrospective study based on propensity score matching (PSM). Association between the triglyceride glucose-body roundness index and the incidence of cardiovascular disease among Chinese middle and old-aged adults: a nationwide prospective cohort study. FTZ alleviates lipid deposition in diabetic kidney disease by AMPK/ACC/SREBP signaling pathway.
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