PMID:18492766

Citation	Wu, Y and Smas, CM (2008) Wdnm1-like, a new adipokine with a role in MMP-2 activation. Am. J. Physiol. Endocrinol. Metab. 295:E205-15
Abstract	White adipose tissue functions in energy storage and as an endocrine organ. DNA microarray analysis led us to identify Wdnm1-like, a distant member of the whey acidic protein/four-disulfide core (WAP/4-DSC) family, as a differentiation-dependent gene in white and brown adipogenesis. Wdnm1-like is a novel 6.8-kDa protein, and Western blot analysis reveals secretion into culture media. Wdnm1-like transcript is selectively expressed in adipose tissue and liver and is enriched approximately 500-fold in white adipose depots vs. brown. Cellular fractionation of WAT demonstrates Wdnm1-like transcript expression is restricted to the adipocyte population. Studies in 3T3-L1 preadipocytes, an in vitro model of white adipogenesis, indicate Wdnm1-like transcript increases within 6 h of adipogenic induction with an approximately 17,000-fold increase by day 7. Dramatic upregulation of Wdnm1-like also accompanies white adipogenesis of ScAP-23 preadipocytes and primary preadipocytes. TNF-alpha treatment of 3T3-L1 adipocytes increased Wdnm1-like transcript level 2.4-fold and was attenuated by pretreatment with the p38 MAP kinase inhibitor SB203580. A number of WAP/4-DSC family proteins function as protease inhibitors. This, taken with the role of extracellular remodeling in adipogenesis, led us to address effects of Wdnm1-like on matrix metalloproteinase (MMP) activity. Gelatin zymography of HT1080 fibrosarcoma cells transfected with a Wdnm1-like expression construct revealed markedly increased levels of active MMP-2. Our findings identify a new member of the adipocyte "secretome" that functions to enhance MMP-2 activity. We postulate that Wdnm1-like may play roles in remodeling of the extracellular milieu in adipogenesis, as well as in tumor microenvironments where adipocytes are key stromal components.
Links	PubMed PMC2493586 Online version:10.1152/ajpendo.90316.2008
Keywords	3T3-L1 Cells; Adipocytes, Brown/enzymology; Adipocytes, Brown/metabolism; Adipogenesis/physiology; Adipokines/biosynthesis; Adipokines/genetics; Adipokines/metabolism; Adipose Tissue, White/enzymology; Adipose Tissue, White/metabolism; Amino Acid Sequence; Animals; Base Sequence; Blotting, Northern; Enzyme Activation; Male; Matrix Metalloproteinase 2/metabolism; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Oligonucleotide Array Sequence Analysis; RNA, Messenger/biosynthesis; RNA, Messenger/genetics; Reverse Transcriptase Polymerase Chain Reaction; Sequence Alignment; Transcription, Genetic; Transfection
edit table

Annotations

Gene product	Qualifier	GO ID	GO term name	Evidence Code	with/from	Aspect	Notes	Status
edit table

References

See Help:References for how to manage references in GONUTS.