RXR antagonism induces G 0/G 1 cell cycle arrest and ameliorates obesity by up-regulating the p53-p21 Cip1 pathway in adipocytes

Journal of Pathology

Volumn 226, Issue 5, 2012, Pages 784-795

  Nakatsuka, Atsuko ^a   Wada, Jun ^a   Hida, Kazuyuki ^a   Hida, Aya ^a   Eguchi, Jun ^a   Teshigawara, Sanae ^a   Murakami, Kazutoshi ^a   Kanzaki, Motoko ^a   Inoue, Kentaro ^a   Terami, Takahiro ^a   Katayama, Akihiro ^a   Ogawa, Daisuke ^a   Kagechika, Hiroyuki ^b   Makino, Hirofumi ^a  

^a OKAYAMA UNIVERSITY   (Japan)

^b TOKYO MEDICAL AND DENTAL UNIVERSITY   (Japan)

Author keywords

Cell cycle; Nuclear receptors; Obesity; p21; p53; RXR

Indexed keywords

ANTIDIABETIC AGENT; ANTIOBESITY AGENT; CYCLIN D1; CYCLIN DEPENDENT KINASE INHIBITOR 1; HX 531; PROTEIN P53; RETINOID X RECEPTOR; S PHASE KINASE ASSOCIATED PROTEIN 2; SHORT HAIRPIN RNA; UNCLASSIFIED DRUG;

ADIPOCYTE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL CULTURE; CELL CYCLE G0 PHASE; CELL PROLIFERATION; CELL SIZE; CONTROLLED STUDY; G1 PHASE CELL CYCLE CHECKPOINT; HUMAN; HUMAN CELL; HYPERTROPHY; IN VIVO STUDY; LENTIVIRINAE; MALE; NONHUMAN; OBESITY; PRIORITY JOURNAL; PROADIPOCYTE; RAT; RENAL PROTECTION; SIGNAL TRANSDUCTION; UPREGULATION;

ADIPOCYTES; ANIMALS; ANTI-OBESITY AGENTS; BENZOIC ACIDS; BIPHENYL COMPOUNDS; CELL PROLIFERATION; CELL SIZE; CELLS, CULTURED; CYCLIN-DEPENDENT KINASE INHIBITOR P21; DIABETES MELLITUS, TYPE 2; DISEASE MODELS, ANIMAL; G0 PHASE; G1 PHASE CELL CYCLE CHECKPOINTS; HUMANS; HYPERTROPHY; HYPOGLYCEMIC AGENTS; KIDNEY GLOMERULUS; MALE; OBESITY; PPAR GAMMA; RATS; RATS, INBRED OLETF; RETINOID X RECEPTORS; RNA INTERFERENCE; SIGNAL TRANSDUCTION; THIAZOLIDINEDIONES; TIME FACTORS; TRANSFECTION; TUMOR SUPPRESSOR PROTEIN P53; UP-REGULATION;

EID: 84858002033     PISSN: 00223417     EISSN: 10969896     Source Type: Journal    
DOI: 10.1002/path.3001     Document Type: Article

References (31)

1. Griffin SV, Pichler R,Wada T, et al. The role of cell cycle proteins in glomerular disease. Semin Nephrol 2003; 23: 569-582. (Pubitemid 38030091)
2. Wolf G, Reinking R, Zahner G, et al. Erk 1,2 phosphorylates p27(Kip1): Functional evidence for a role in high glucose-induced hypertrophy of mesangial cells. Diabetologia 2003; 46: 1090-1099. (Pubitemid 37041239)
3. Abdel-Wahab N, Weston BS, Roberts T, et al. Connective tissue growth factor and regulation of the mesangial cell cycle: role in cellular hypertrophy. J Am Soc Nephrol 2002; 13: 2437-2445.
4. Al-Douahji M, Brugarolas J, Brown PA, et al. The cyclin kinase inhibitor p21WAF1/CIP1 is required for glomerular hypertrophy in experimental diabetic nephropathy. Kidney Int 1999; 56: 1691-1699. (Pubitemid 29518169)
5. Wolf G, Schroeder R, Thaiss F, et al. Glomerular expression of p27Kip1 in diabetic db/db mouse: role of hyperglycemia. Kidney Int 1998; 53: 869-879. (Pubitemid 28155659)
6. Wolf G, Schanze A, Stahl RA, et al. p27(Kip1) Knockout mice are protected from diabetic nephropathy: evidence for p27(Kip1) haplotype insufficiency. Kidney Int 2005; 68: 1583-1589. (Pubitemid 43169903)
7. Sakai T, Sakaue H, Nakamura T, et al. Skp2 controls adipocyte proliferation during the development of obesity. J Biol Chem 2007; 282: 2038-2046. (Pubitemid 47076733)
8. Naaz A, Holsberger DR, Iwamoto GA, et al. Loss of cyclin-dependent kinase inhibitors produces adipocyte hyperplasia and obesity. FASEB J 2004; 18: 1925-1927. (Pubitemid 39602286)
9. Inoue N, Yahagi N, Yamamoto T, et al. Cyclin-dependent kinase inhibitor, p21WAF1/CIP1, is involved in adipocyte differentiation and hypertrophy, linking to obesity, and insulin resistance. J Biol Chem 2008; 283: 21220-21229.
10. Yahagi N, Shimano H, Matsuzaka T, et al. p53 Activation in adipocytes of obese mice. J Biol Chem 2003; 278: 25395-25400. (Pubitemid 36835289)
11. Hallenborg P, Feddersen S, Madsen L, et al. The tumor suppressors pRB and p53 as regulators of adipocyte differentiation and function. Expert Opin Ther Targets 2009; 13: 235-246.
12. Bazuine M, Stenkula KG, Cam M, et al. Guardian of corpulence: a hypothesis on p53 signaling in the fat cell. Clin Lipidol 2009; 4: 231-243.
13. Pinaire JA, Reifel-Miller A. Therapeutic potential of retinoid x receptor modulators for the treatment of the metabolic syndrome. PPAR Res 2007; 2007: 94156.
14. Altucci L, Leibowitz MD, Ogilvie KM, et al. RAR and RXR modulation in cancer and metabolic disease. Nat Rev Drug Discov 2007; 6: 793-810. (Pubitemid 47504871)
15. Shulman AI, Mangelsdorf DJ. Retinoid x receptor heterodimers in the metabolic syndrome. N Engl J Med 2005; 353: 604-615. (Pubitemid 41138942)
16. Imai T, Jiang M, Chambon P, et al. Impaired adipogenesis and lipolysis in the mouse upon selective ablation of the retinoid X receptor-α mediated by a tamoxifen-inducible chimeric Cre recombinase (Cre-ERT2) in adipocytes. Proc Natl Acad Sci USA 2001; 98: 224-228. (Pubitemid 32095891)
17. Yamauchi T, Waki H, Kamon J, et al. Inhibition of RXR and PPARγ ameliorates diet-induced obesity and type 2 diabetes. J Clin Invest 2001; 108: 1001-1013. (Pubitemid 32946074)
18. Ebisawa M, Umemiya H, Ohta K, et al. Retinoid X receptor-antagonistic diazepinylbenzoic acids. Chem Pharm Bull (Tokyo) 1999; 47: 1778-1786. (Pubitemid 30020563)
19. Tanaka T, Suh KS, Lo AM, et al. p21WAF1/CIP1 is a common transcriptional target of retinoid receptors: pleiotropic regulatory mechanism through retinoic acid receptor (RAR)/retinoid X receptor (RXR) heterodimer and RXR/RXR homodimer. J Biol Chem 2007; 282: 29987-29997. (Pubitemid 350035294)
20. Bonofiglio D, Cione E, Qi H, et al. Combined low doses of PPARγ and RXR ligands trigger an intrinsic apoptotic pathway in human breast cancer cells. Am J Pathol 2009; 175: 1270-1280.
21. Aouadi M, Jager J, Laurent K, et al. p38MAP Kinase activity is required for human primary adipocyte differentiation. FEBS Lett 2007; 581: 5591-5596. (Pubitemid 350179766)
22. Okada T, Wada J, Hida K, et al. Thiazolidinediones ameliorate diabetic nephropathy via cell cycle-dependent mechanisms. Diabetes 2006; 55: 1666-1677. (Pubitemid 44324119)
23. Barre B, Perkins ND. The Skp2 promoter integrates signaling through the NF-κB, p53, and Akt/GSK3β pathways to regulate autophagy and apoptosis. Mol Cell 2010; 38: 524-538.
24. Mao JH, Perez-Losada J, Wu D, et al. Fbxw7/Cdc4 is a p53- dependent, haploinsufficient tumour suppressor gene. Nature 2004; 432: 775-779. (Pubitemid 39656299)
25. Onoyama I, Nakayama KI. Fbxw7 in cell cycle exit and stem cell maintenance: insight from gene-targeted mice. Cell Cycle 2008; 7: 3307-3313.
26. 1 switch gene 2 regulates adipose lipolysis through association with adipose triglyceride lipase. Cell Metab 2010; 11: 194-205.
27. 1 switch gene 2 is a novel PPAR target gene. Biochem J 2005; 392: 313-324.
28. Kitareewan S, Blumen S, Sekula D, et al. G0S2 is an all-trans-retinoic acid target gene. Int J Oncol 2008; 33: 397-404.
29. Levine AJ. p53, the cellular gatekeeper for growth and division. Cell 1997; 88: 323-331. (Pubitemid 27131374)
30. Hamza MS, Pott S, Vega VB, et al. De novo identification of PPARγ/RXR binding sites and direct targets during adipogenesis. PLoS One 2009; 4: e4907.
31. Hauser S, Adelmant G, Sarraf P, et al. Degradation of the peroxisome proliferator-activated receptor-γ is linked to ligand-dependent activation. J Biol Chem 2000; 275: 18527-18533. (Pubitemid 30414814)