title: Effect of Wnt-1 inducible signaling pathway protein-2 (WISP-2/CCN5), a downstream protein of Wnt signaling, on adipocyte differentiation.
abstract: Wnt signaling negatively regulates adipocyte differentiation, and ectopic expression of Wnt-1 in 3T3-L1 cells induces several downstream molecules of Wnt signaling, including Wnt-1 inducible signaling pathway protein (WISP)-2. In this study, we examined the role of WISP-2 in the process of adipocyte differentiation using an in vitro cell culture system. In the differentiation of 3T3-L1 cells, WISP-2 expression was observed in growing cells and declined thereafter. In the mitotic clonal expansion phase of adipocyte differentiation, WISP-2 expression was transiently down-regulated concurrently with up-regulation of CCAAT/enhancer-binding protein delta expression. Treatment of 3T3-L1 cells in the differentiation medium with lithium, an activator of Wnt signaling, inhibited the differentiation process with concomitant induction of WISP-2. Treatment of differentiated cells with lithium induced de-differentiation as evidenced by profound reduction of peroxisome proliferator-activator receptor gamma expression and concomitant induction of WISP-2. However, de-differentiation of differentiated cells induced by tumor necrosis factor-alpha did not induce WISP-2 expression. To directly examine the effect of WISP-2 on adipocyte differentiation, 3T3-L1 cells were infected with a retrovirus carrying WISP-2. Although forced expression of WISP-2 inhibited preadipocyte proliferation, it had no effect on adipocyte differentiation. Thus, although WISP-2 is a downstream protein of Wnt signaling, the role of WISP-2 on adipocyte differentiation may be marginal, at least in this in vitro culture model.
authors.affiliation: Department of Public Health, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. inadera@med.u-toyama.ac.jp
authors.forename: Hidekuni
authors.initials: H
authors.lastname: Inadera
authors.forename: Akiko
authors.initials: A
authors.lastname: Shimomura
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Tachibana
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008094:Lithium / Q000494:pharmacology; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha; C539089:WISP-2 protein, mouse; D051153:Wnt Proteins; D008094:Lithium; D038362:Glycogen Synthase Kinase 3