期刊
JOURNAL OF MOLECULAR CELL BIOLOGY
卷 6, 期 5, 页码 368-379出版社
OXFORD UNIV PRESS
DOI: 10.1093/jmcb/mju034
关键词
adipogenesis; mesenchymal stem cells; C/EBP alpha; CKIP-1; HDAC1
类别
资金
- Chinese National Basic Research Programs [2011CB910802, 2013CB910803]
- National Key Technologies R&D Program for New Drugs [2014ZX09J14106-04C]
- ICGEB [CRP/CHN13-02]
- Chinese National Natural Science Foundation [31000521, 31125010, 81221004]
Mesenchymal stem cells (MSCs) are considered as the developmental origin of multiple lineage cells including osteocytes, adipocytes, and muscle cells. Previous studies demonstrated that the PH domain-containing protein CKIP-1 plays an important role in the development of osteoblasts and cardiomyocytes. However, whether CKIP-1 is involved in the generation of adipocytes as well as the MSC differentiation remains unknown. Here we show that CKIP-1 is a novel regulator of MSCs differentiating into adipocytes. MSCs derived from CKIP-1-deficient mice display enhanced adipogenesis upon induction. Further analysis showed that CKIP-1 interacts with the histone deacetylase HDAC1 in the nucleus and inhibits the transcription of CCAAT/enhancer-binding protein alpha (C/EBP alpha), which is a crucial adipogenic transcription factor. Ectopic expression of CKIP-1 in a MSC-like cell line C3H/10T1/2 reduced the generation of adipocytes due to suppression of adipogenic factors, including C/EBP alpha. Moreover, CKIP-1-deficient miceshowed an increase in body weight and white adipose tissue gains when fed on a high-fat diet. Collectively, these results suggest that CKIP-1 is a novel inhibitor of MSC-originated adipogenesis by enhancing HDAC1-associated repression of C/EBP alpha.
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