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CTSB promotes porcine preadipocytes differentiation by degrading fibronectin and attenuating the Wnt/β-catenin signaling pathway

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Abstract

The process of preadipocytes differentiation plays a vital role in adipose tissue expansion and many factors are involved in this event. Cathepsin B (CTSB), secreted from lysosome, has been reported in regulating a variety of physiological processes. In this study, we demonstrated CTSB promotes lipid accumulation and adipogenic genes expression in porcine primary preadipocytes by degrading fibronectin (Fn), a key component of extracellular matrix. Lithium chloride (LiCl) is an activator of Wnt/β-catenin signaling through stabilizing β-catenin. We found that CTSB can relieve the anti-adipogenic effects of LiCl, indicating that CTSB could impact Wnt/β-catenin signaling pathway. Interestingly, Fn is an important target gene of Wnt/β-catenin. So we considered that CTSB promote preadipocytes differentiation by suppressing these two pathways.

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References

  1. Bulcao C, Ferreira SR, Giuffrida F, Ribeiro-Filho FF (2006) The new adipose tissue and adipocytokines. Curr Diabetes Rev 2:19–28

    Article  CAS  PubMed  Google Scholar 

  2. Gandhi H, Upaganlawar A, Balaraman R (2010) Adipocytokines: the pied pipers. J Pharmacol Pharmacother 1:9–17

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Krysiak R, Okopień B, Herman ZS (2005) Adipose tissue: a new endocrine organ. Przegl Lek 62:919–923

    PubMed  Google Scholar 

  4. Chun T-H (2012) Peri-adipocyte ECM remodeling in obesity and adipose tissue fibrosis. Adipocyte 1:89–95

    Article  PubMed Central  PubMed  Google Scholar 

  5. Hirsch J, Batchelor B (1976) Adipose tissue cellularity in human obesity. Clin Endocrinol Metab 5:299–311

    Article  CAS  PubMed  Google Scholar 

  6. Gregor MF, Hotamisligil GS (2011) Inflammatory mechanisms in obesity. Annu Rev Immunol 29:415–445

    Article  CAS  PubMed  Google Scholar 

  7. Lumeng CN, Saltiel AR (2011) Inflammatory links between obesity and metabolic disease. J Clin Invest 121:2111

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Schenk S, Saberi M, Olefsky JM (2008) Insulin sensitivity: modulation by nutrients and inflammation. J Clin Invest 118:2992–3002

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Nakajima I, Muroya S, Tanabe R-I, Chikuni K (2002) Extracellular matrix development during differentiation into adipocytes with a unique increase in type V and VI collagen. Biol Cell 94:197–203

    Article  CAS  PubMed  Google Scholar 

  10. Antras J, Hilliou F, Redziniak G, Pairault J (1989) Decreased biosynthesis of actin and cellular fibronectin during adipose conversion of 3T3-F442A cells. Reorganization of the cytoarchitecture and extracellular matrix fibronectin. Biol Cell 66:247–254

    Article  CAS  PubMed  Google Scholar 

  11. Rodríguez Fernández JL, Ben-Ze’ev A (1989) Regulation of fibronectin, integrin and cytoskeleton expression in differentiating adipocytes: inhibition by extracellular matrix and polylysine. Differentiation 42:65–74

    Article  PubMed  Google Scholar 

  12. Spiegelman BM, Ginty CA (1983) Fibronectin modulation of cell shape and lipogenic gene expression in 3T3-adipocytes. Cell 35:657–666

    Article  CAS  PubMed  Google Scholar 

  13. Brix K, Dunkhorst A, Mayer K, Jordans S (2008) Cysteine cathepsins: cellular roadmap to different functions. Biochimie 90:194–207

    Article  CAS  PubMed  Google Scholar 

  14. Conus S, Simon H-U (2008) Cathepsins: key modulators of cell death and inflammatory responses. Biochem Pharmacol 76:1374–1382

    Article  CAS  PubMed  Google Scholar 

  15. Tardy C, Codogno P, Autefage H et al (2006) Lysosomes and lysosomal proteins in cancer cell death (new players of an old struggle). Biochim Biophys Acta 1765:101–125

    CAS  PubMed  Google Scholar 

  16. Zava\vsnik-Bergant T, Turk B (2007) Cysteine proteases: destruction ability versus immunomodulation capacity in immune cells. Biol Chem 388:1141–1149

    Google Scholar 

  17. Chavey C, Mari B, Monthouel M-N et al (2003) Matrix metalloproteinases are differentially expressed in adipose tissue during obesity and modulate adipocyte differentiation. J Biol Chem 278:11888–11896

    Article  CAS  PubMed  Google Scholar 

  18. Taleb S, Lacasa D, Bastard J-P et al (2005) Cathepsin S, a novel biomarker of adiposity: relevance to atherogenesis. FASEB J 19:1540–1542

    CAS  PubMed  Google Scholar 

  19. Taleb S, Cancello R, Clément K, Lacasa D (2006) Cathepsin s promotes human preadipocyte differentiation: possible involvement of fibronectin degradation. Endocrinology 147:4950–4959

    Article  CAS  PubMed  Google Scholar 

  20. Masson O, Prébois C, Derocq D et al (2011) Cathepsin-D, a key protease in breast cancer, is up-regulated in obese mouse and human adipose tissue, and controls adipogenesis. PLoS One 6:e16452

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Chiellini C, Costa M, Novelli SE et al (2003) Identification of cathepsin K as a novel marker of adiposity in white adipose tissue. J Cell Physiol 195:309–321

    Article  CAS  PubMed  Google Scholar 

  22. Funicello M, Novelli M, Ragni M et al (2007) Cathepsin K null mice show reduced adiposity during the rapid accumulation of fat stores. PLoS One 2:e683

    Article  PubMed Central  PubMed  Google Scholar 

  23. Withana NP, Blum G, Sameni M et al (2012) Cathepsin B inhibition limits bone metastasis in breast cancer. Cancer Res 72:1199–1209

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Cavallo-Medved D, Rudy D, Blum G et al (2009) Live-cell imaging demonstrates extracellular matrix degradation in association with active cathepsin B in caveolae of endothelial cells during tube formation. Exp Cell Res 315:1234–1246

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Wong WP, Altemus JB, Hester JF et al (2013) Cathepsin B is a novel gender-dependent determinant of cholesterol absorption from the intestine. J Lipid Res 54:816–822

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Morchang A, Panaampon J, Suttitheptumrong A et al (2013) Role of cathepsin B in dengue virus-mediated apoptosis. Biochem Biophys Res Commun 438:20–25

    Article  CAS  PubMed  Google Scholar 

  27. Tatti M, Motta M, Di Bartolomeo S et al (2013) Cathepsin-mediated regulation of autophagy in saposin C deficiency. Autophagy 9:241–243

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Freese JL, Pino D, Pleasure SJ (2010) Wnt signaling in development and disease. Neurobiol Dis 38:148–153

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Lefterova MI, Lazar MA (2009) New developments in adipogenesis. Trends Endocrinol Metab 20:107–114

    Article  CAS  PubMed  Google Scholar 

  30. Rosen ED, MacDougald OA (2006) Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol 7:885–896

    Article  CAS  PubMed  Google Scholar 

  31. He XC, Zhang J, Tong W-G et al (2004) BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt–β-catenin signaling. Nat Genet 36:1117–1121

    Article  CAS  PubMed  Google Scholar 

  32. Logan CY, Nusse R (2004) The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 20:781–810

    Article  CAS  PubMed  Google Scholar 

  33. Luo J, Deng Z-L, Luo X et al (2007) A protocol for rapid generation of recombinant adenoviruses using the AdEasy system. Nat Protoc 2:1236–1247

    Article  CAS  PubMed  Google Scholar 

  34. De Langhe SP, Sala FG, Del Moral P-M et al (2005) Dickkopf-1 (DKK1) reveals that fibronectin is a major target of Wnt signaling in branching morphogenesis of the mouse embryonic lung. Dev Biol 277:316–331

    Article  PubMed  Google Scholar 

  35. Ten Berge D, Koole W, Fuerer C et al (2008) Wnt signaling mediates self-organization and axis formation in embryoid bodies. Cell Stem Cell 3:508–518

    Article  PubMed Central  PubMed  Google Scholar 

  36. Eguchi A, Feldstein AE (2013) Lysosomal Cathepsin D contributes to cell death during adipocyte hypertrophy. Adipocyte 2:0–1

    Article  Google Scholar 

  37. Naour N, Rouault C, Fellahi S et al (2010) Cathepsins in human obesity: changes in energy balance predominantly affect cathepsin s in adipose tissue and in circulation. J Clin Endocrinol Metab 95:1861–1868

    Article  CAS  PubMed  Google Scholar 

  38. Xiao Y, Junfeng H, Tianhong L et al (2006) Cathepsin K in adipocyte differentiation and its potential role in the pathogenesis of obesity. J Clin Endocrinol Metab 91:4520–4527

    Article  PubMed  Google Scholar 

  39. Yang M, Zhang Y, Pan J et al (2007) Cathepsin L activity controls adipogenesis and glucose tolerance. Nat Cell Biol 9:970–977

    CAS  PubMed  Google Scholar 

  40. Li S, Du L, Zhang L et al (2013) Cathepsin B contributes to autophagy-related 7 (Atg7)-induced nod-like receptor 3 (NLRP3)-dependent proinflammatory response and aggravates lipotoxicity in rat insulinoma cell line. J Biol Chem 288:30094–30104

    Article  CAS  PubMed  Google Scholar 

  41. Santoni M, Amantini C, Morelli MB, et al (2013) Effect of sunitinib and pazopanib on necrosis and autophagic cell death in cancer cells: role of cathepsin B. J Clin Oncol. Abstr. p e15513

  42. Li XJ, Yang H, Li GX et al (2012) Transcriptome profile analysis of porcine adipose tissue by high-throughput sequencing. Anim Genet 43:144–152

    Article  CAS  PubMed  Google Scholar 

  43. Gregoire FM, Smas CM, Sul HS (1998) Understanding adipocyte differentiation. Physiol Rev 78:783–809

    CAS  PubMed  Google Scholar 

  44. Antras-Ferry J, Hilliou F, Lasnier F, Pairault J (1994) Forskolin induces the reorganization of extracellular matrix fibronectin and cytoarchitecture in 3T3-F442A adipocytes: its effect on fibronectin gene expression. Biochim Biophys Acta 1222:390–394

    Article  CAS  PubMed  Google Scholar 

  45. Bortell R, Owen TA, Ignotz R et al (1994) TGFβ1 prevents the down-regulation of type I procollagen, fibronectin, and TGFβ1 gene expression associated with 3T3-L1 pre-adipocyte differentiation. J Cell Biochem 54:256–263

    Article  CAS  PubMed  Google Scholar 

  46. Weiner FR, Shah A, Smith PJ et al (1989) Regulation of collagen gene expression in 3T3-L1 cells. Effects of adipocyte differentiation and tumor necrosis factor alpha. Biochemistry 28:4094–4099

    Article  CAS  PubMed  Google Scholar 

  47. Ross SE, Hemati N, Longo KA et al (2000) Inhibition of adipogenesis by Wnt signaling. Science 289:950–953

    Article  CAS  PubMed  Google Scholar 

  48. Vertino AM, Taylor-Jones JM, Longo KA et al (2005) Wnt10b deficiency promotes coexpression of myogenic and adipogenic programs in myoblasts. Mol Biol Cell 16:2039–2048

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Vangipuram SD, Sheele J, Atkinson RL et al (2004) A human adenovirus enhances preadipocyte differentiation. Obes Res 12:770–777

    Article  CAS  PubMed  Google Scholar 

  50. Wang Y, Zhao L, Smas C, Sul HS (2010) Pref-1 interacts with fibronectin to inhibit adipocyte differentiation. Mol Cell Biol 30:3480–3492

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This work was funded by grants from the National Natural Science Foundation of China (No. 31272410), the National Basic Research Program of China (No. 2012CB124705), the Program for Innovative Research Team in the Northwest A&F University, and the National Swine Industry Technology System (No. CARS-36-04B).

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  1. Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, 22 Xinong Road, Yangling, 712100, People’s Republic of China

    Zhen-Yu Zhang, Yin Mai, Hao Yang, Pei-Yue Dong, Xue-Li Zheng & Gong-She Yang

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  1. Zhen-Yu Zhang
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Correspondence to Gong-She Yang.

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Zhang, ZY., Mai, Y., Yang, H. et al. CTSB promotes porcine preadipocytes differentiation by degrading fibronectin and attenuating the Wnt/β-catenin signaling pathway. Mol Cell Biochem 395, 53–64 (2014). https://doi.org/10.1007/s11010-014-2111-6

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