PMID- 37392202
OWN - NLM
STAT- MEDLINE
DCOM- 20230927
LR  - 20240402
IS  - 1432-5233 (Electronic)
IS  - 0940-5429 (Linking)
VI  - 60
IP  - 11
DP  - 2023 Nov
TI  - The CEBPA-FGF21 regulatory network may participate in the T2DM-induced skeletal 
      muscle atrophy by regulating the autophagy-lysosomal pathway.
PG  - 1491-1503
LID - 10.1007/s00592-023-02131-x [doi]
AB  - 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.
CI  - (c) 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.
FAU - Wu, Kai
AU  - Wu K
AD  - Department of Physical Medicine and Rehabilitation, Xiangya Hospital of Central 
      South University, No. 87, Xiang-Ya Road, Changsha, 410008, Hunan Province, China.
AD  - National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of 
      Central South University, Changsha, 410008, Hunan Province, China.
FAU - Huang, Sha
AU  - Huang S
AD  - National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of 
      Central South University, Changsha, 410008, Hunan Province, China.
AD  - Department of Neurology, Xiangya Hospital of Central South University, Changsha, 
      410008, China.
FAU - Zheng, Fan
AU  - Zheng F
AD  - National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of 
      Central South University, Changsha, 410008, Hunan Province, China.
AD  - Health Management Department, Xiangya Hospital of Central South University, 
      Changsha, 410008, China.
FAU - Liu, Yuan
AU  - Liu Y
AD  - Department of Physical Medicine and Rehabilitation, Xiangya Hospital of Central 
      South University, No. 87, Xiang-Ya Road, Changsha, 410008, Hunan Province, China. 
      seuyuanliu@csu.edu.cn.
AD  - National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of 
      Central South University, Changsha, 410008, Hunan Province, China. 
      seuyuanliu@csu.edu.cn.
LA  - eng
GR  - 81702241/National Natural Science Foundation of China/
GR  - 2018JJ3847/the Natural Science Foundation of Hunan Province/
GR  - 2020M682597/China Postdoctoral Science Foundation/
GR  - 2021JJ31129/the Natural Science Foundation of Hunan Province/
PT  - Journal Article
DEP - 20230701
PL  - Germany
TA  - Acta Diabetol
JT  - Acta diabetologica
JID - 9200299
RN  - 0 (fibroblast growth factor 21)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Rats
MH  - Animals
MH  - *Diabetes Mellitus, Type 2/complications/genetics/metabolism
MH  - Muscular Atrophy/genetics/metabolism
MH  - Muscle, Skeletal/metabolism
MH  - Autophagy/genetics
MH  - RNA, Messenger/metabolism
MH  - Transcription Factors
MH  - Lysosomes
OTO - NOTNLM
OT  - Autophagy-lysosomal pathway
OT  - CEBPA
OT  - FGF21
OT  - Skeletal muscle atrophy
OT  - Transcription factor
OT  - Type 2 diabetes mellitus
EDAT- 2023/07/01 21:07
MHDA- 2023/09/27 06:42
CRDT- 2023/07/01 11:03
PHST- 2022/11/15 00:00 [received]
PHST- 2023/06/05 00:00 [accepted]
PHST- 2023/09/27 06:42 [medline]
PHST- 2023/07/01 21:07 [pubmed]
PHST- 2023/07/01 11:03 [entrez]
AID - 10.1007/s00592-023-02131-x [pii]
AID - 10.1007/s00592-023-02131-x [doi]
PST - ppublish
SO  - Acta Diabetol. 2023 Nov;60(11):1491-1503. doi: 10.1007/s00592-023-02131-x. Epub 
      2023 Jul 1.