PMID- 28123643
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1943-8141 (Print)
IS  - 1943-8141 (Electronic)
IS  - 1943-8141 (Linking)
VI  - 9
IP  - 1
DP  - 2017
TI  - GSK3beta activity is essential for senescence-associated heterochromatin foci (SAHF) 
      formation induced by HMGA2 in WI38 cells.
PG  - 167-174
AB  - Cellular senescence is an irreversible form of cell cycle arrest, which is often 
      characterized by domains of facultative heterochromatin substructures also known 
      as senescence-associated heterochromatin foci (SAHF). SAHF assembly is likely 
      mediated through the downregulation of the Wnt pathway, which inhibits Glycogen 
      Synthase Kinase 3 Beta (GSK3beta) in cells undergoing replicative senescence. 
      Alternatively, High Mobility Group AT-Hook 2 (HMGA2) can also induce SAHF 
      formation in primary cells, through a process in which the involved cell 
      signaling pathway is unknown. Accordingly, it is important to determine whether 
      GSK3beta and the Wnt pathway are necessary during HMGA2-induced SAHF formation. In 
      this study, we developed a senescence model for SAHF assembly in WI38 cell 
      through ectopic expression of HMGA2. In this model, typical senescent features 
      were identified, including elevated SA-beta-galactosidase staining and the 
      downregulation of the Wnt pathway. We also showed that the GSK3beta inhibitor LiCl 
      can partly disable SAHF formation through the HMGA2 overexpression in WI38 cells. 
      However, the disabled SAHF formation resulting from the inactivity of GSK3beta in 
      our senescence model cannot be restored through ectopic overexpression of Catenin 
      Beta 1 (CTNNB1), a downstream transcription factor of the Wnt pathway. This 
      indicates that the GSK3beta activity alone, and not those of downstream target 
      genes, is crucial for the HMGA2-induced SAHF formation following the 
      downregulation of the Wnt pathway.
FAU - Shi, Xi
AU  - Shi X
AD  - The Institute of Audiology and Balance Science of Xuzhou Medical University 
      Xuzhou 221004, China.
FAU - Tian, Baoqing
AU  - Tian B
AD  - Institute of Bioengineering of Jinan University Guangzhou 510632, China.
FAU - Ma, Chi
AU  - Ma C
AD  - The Institute of Genetics and Cytology, Northeast Normal University Changchun 
      130024, China.
FAU - Liu, Lingxia
AU  - Liu L
AD  - The Institute of Genetics and Cytology, Northeast Normal University Changchun 
      130024, China.
FAU - Zhang, Na
AU  - Zhang N
AD  - The Institute of Genetics and Cytology, Northeast Normal University Changchun 
      130024, China.
FAU - Na, Yuan
AU  - Na Y
AD  - The Institute of Audiology and Balance Science of Xuzhou Medical University 
      Xuzhou 221004, China.
FAU - Li, Jing
AU  - Li J
AD  - State Key Laboratory of Protein and Plant Gene Research, College of Life Science, 
      Peking University Beijing 100871, China.
FAU - Lu, Jun
AU  - Lu J
AD  - The Institute of Genetics and Cytology, Northeast Normal University Changchun 
      130024, China.
FAU - Qiao, Yuehua
AU  - Qiao Y
AD  - Clinical Hearing Center of Affiliated Hospital of Xuzhou Medical University 
      Xuzhou 221006, China.
LA  - eng
PT  - Journal Article
DEP - 20170115
PL  - United States
TA  - Am J Transl Res
JT  - American journal of translational research
JID - 101493030
PMC - PMC5250713
OTO - NOTNLM
OT  - GSK3beta
OT  - HMGA2
OT  - SAHF
OT  - Wnt2
EDAT- 2017/01/27 06:00
MHDA- 2017/01/27 06:01
PMCR- 2017/01/15
CRDT- 2017/01/27 06:00
PHST- 2016/07/17 00:00 [received]
PHST- 2016/12/02 00:00 [accepted]
PHST- 2017/01/27 06:00 [entrez]
PHST- 2017/01/27 06:00 [pubmed]
PHST- 2017/01/27 06:01 [medline]
PHST- 2017/01/15 00:00 [pmc-release]
PST - epublish
SO  - Am J Transl Res. 2017 Jan 15;9(1):167-174. eCollection 2017.