title: CKIP-1 suppresses the adipogenesis of mesenchymal stem cells by enhancing HDAC1-associated repression of C/EBPα.
abstract: 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 α (C/EBPα), 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/EBPα. Moreover, CKIP-1-deficient mice showed 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/EBPα.
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China Beijing Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Dahu
authors.initials: D
authors.lastname: Li
authors.affiliation: Beijing Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Li
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China.
authors.forename: Guichun
authors.initials: G
authors.lastname: Xing
authors.affiliation: Laboratory Animal Center of the Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Lanzhi
authors.initials: L
authors.lastname: Ma
authors.affiliation: Laboratory Animal Center of the Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Lujing
authors.initials: L
authors.lastname: Ding
authors.affiliation: Beijing Institute of Basic Medical Sciences, Beijing 100850, China zhanglq@nic.bmi.ac.cn hefc@nic.bmi.ac.cn zhangyi612@hotmail.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China zhanglq@nic.bmi.ac.cn hefc@nic.bmi.ac.cn zhangyi612@hotmail.com.
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China zhanglq@nic.bmi.ac.cn hefc@nic.bmi.ac.cn zhangyi612@hotmail.com.
authors.forename: Lingqiang
authors.initials: L
authors.lastname: Zhang
mesh_terms: D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D056284:Histone Deacetylase 1 / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047908:Intracellular Signaling Peptides and Proteins
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins; D056284:Histone Deacetylase 1; C530718:CEBPA protein, mouse; C484389:Hdac1 protein, mouse; C000620556:PLEKHO1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins
keywords: C/EBPα, CKIP-1; HDAC1; adipogenesis; mesenchymal stem cells