PMID- 35476671
OWN - NLM
STAT- MEDLINE
DCOM- 20220511
LR  - 20220716
IS  - 1545-7885 (Electronic)
IS  - 1544-9173 (Print)
IS  - 1544-9173 (Linking)
VI  - 20
IP  - 4
DP  - 2022 Apr
TI  - Optineurin promotes myogenesis during muscle regeneration in mice by autophagic 
      degradation of GSK3beta.
PG  - e3001619
LID - 10.1371/journal.pbio.3001619 [doi]
LID - e3001619
AB  - Skeletal muscle regeneration is essential for maintaining muscle function in 
      injury and muscular disease. Myogenesis plays key roles in forming new myofibers 
      during the process. Here, through bioinformatic screen for the potential 
      regulators of myogenesis from 5 independent microarray datasets, we identify an 
      overlapping differentially expressed gene (DEG) optineurin (OPTN). Optn knockdown 
      (KD) delays muscle regeneration in mice and impairs C2C12 myoblast 
      differentiation without affecting their proliferation. Conversely, Optn 
      overexpression (OE) promotes myoblast differentiation. Mechanistically, OPTN 
      increases nuclear levels of beta-catenin and enhances the T-cell factor/lymphoid 
      enhancer factor (TCF/LEF) transcription activity, suggesting activation of Wnt 
      signaling pathway. The activation is accompanied by decreased protein levels of 
      glycogen synthase kinase 3beta (GSK3beta), a negative regulator of the pathway. We 
      further show that OPTN physically interacts with and targets GSK3beta for autophagic 
      degradation. Pharmacological inhibition of GSK3beta rescues the impaired myogenesis 
      induced by Optn KD during muscle regeneration and myoblast differentiation, 
      corroborating that GSK3beta is the downstream effector of OPTN-mediated myogenesis. 
      Together, our study delineates the novel role of OPTN as a potential regulator of 
      myogenesis and may open innovative therapeutic perspectives for muscle 
      regeneration.
FAU - Shi, Xiao Chen
AU  - Shi XC
AD  - Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, 
      College of Animal Science and Technology, Northwest A&F University, Yangling, 
      China.
FAU - Xia, Bo
AU  - Xia B
AUID- ORCID: 0000-0002-4041-9151
AD  - Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, 
      College of Animal Science and Technology, Northwest A&F University, Yangling, 
      China.
FAU - Zhang, Jian Feng
AU  - Zhang JF
AD  - Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, 
      College of Animal Science and Technology, Northwest A&F University, Yangling, 
      China.
FAU - Zhang, Rui Xin
AU  - Zhang RX
AD  - Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, 
      College of Animal Science and Technology, Northwest A&F University, Yangling, 
      China.
FAU - Zhang, Dan Yang
AU  - Zhang DY
AD  - Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, 
      College of Animal Science and Technology, Northwest A&F University, Yangling, 
      China.
FAU - Liu, Huan
AU  - Liu H
AD  - Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, 
      College of Animal Science and Technology, Northwest A&F University, Yangling, 
      China.
FAU - Xie, Bao Cai
AU  - Xie BC
AUID- ORCID: 0000-0003-0611-0131
AD  - Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, 
      College of Animal Science and Technology, Northwest A&F University, Yangling, 
      China.
FAU - Wang, Yong Liang
AU  - Wang YL
AD  - Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, 
      College of Animal Science and Technology, Northwest A&F University, Yangling, 
      China.
FAU - Wu, Jiang Wei
AU  - Wu JW
AUID- ORCID: 0000-0002-6183-6368
AD  - Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, 
      College of Animal Science and Technology, Northwest A&F University, Yangling, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20220427
PL  - United States
TA  - PLoS Biol
JT  - PLoS biology
JID - 101183755
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Optn protein, mouse)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Gsk3b protein, mouse)
SB  - IM
MH  - Animals
MH  - *Autophagy
MH  - *Cell Cycle Proteins/genetics/metabolism
MH  - Cell Differentiation/genetics
MH  - *Glycogen Synthase Kinase 3 beta/genetics/metabolism
MH  - *Membrane Transport Proteins/genetics/metabolism
MH  - Mice
MH  - *Muscle Development/genetics
MH  - Muscle, Skeletal/metabolism
MH  - *Wnt Signaling Pathway/genetics
PMC - PMC9084533
COIS- The authors have declared that no competing interests exist.
EDAT- 2022/04/28 06:00
MHDA- 2022/05/12 06:00
PMCR- 2022/04/27
CRDT- 2022/04/27 17:10
PHST- 2021/10/14 00:00 [received]
PHST- 2022/04/04 00:00 [accepted]
PHST- 2022/05/09 00:00 [revised]
PHST- 2022/04/28 06:00 [pubmed]
PHST- 2022/05/12 06:00 [medline]
PHST- 2022/04/27 17:10 [entrez]
PHST- 2022/04/27 00:00 [pmc-release]
AID - PBIOLOGY-D-21-02724 [pii]
AID - 10.1371/journal.pbio.3001619 [doi]
PST - epublish
SO  - PLoS Biol. 2022 Apr 27;20(4):e3001619. doi: 10.1371/journal.pbio.3001619. 
      eCollection 2022 Apr.