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Adipose tissue behavior is distinctly regulated by neighboring cells and fluid flow stress: a possible role of adipose tissue in peritoneal fibrosis

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Abstract

Adipose tissue, together with the mesothelial layer and microvessels, is a major component of the mesenteric peritoneum, and the mesenterium is a target site for peritoneal fibrosis. Adipose tissue has been speculated to play a role in peritoneal dialysis (PD)-related fibrosis, but the precise cellular kinetics of adipose tissue during this process remain to be determined. To clarify this critical issue, we analyzed the kinetics of adipose tissue using a novel peritoneal reconstruction model in which the effects of mesothelial cells or endothelial cells could be identified. Adipose tissue was co-cultured with mesothelial cells or endothelial cells in a combined organ culture and fluid flow stress culture system. Spindle mesenchymal cells and immature adipocytes derived from adipose tissue were characterized by immunohistochemistry. Adipose tissue fragments cultured in this system yielded many spindle mesenchymal cells in non-co-culture conditions. However, the number of spindle mesenchymal cells emerging from adipose tissue was reduced in co-culture conditions with a covering layer of mesothelial cells. Mesothelial cells co-cultured in the separated condition did not inhibit the emergence of spindle mesenchymal cells from adipose tissue. Interestingly, endothelial cells promoted the emergence of lipid-laden immature adipocytes from adipose tissue under fluid flow stress. We have demonstrated that adipose tissue behavior is not only regulated by mesothelial cells and endothelial cells under fluid flow stress, but is also involved in fibrosis and fat mass production in the peritoneum. Our findings suggest that adipose tissue is a potential source of cells for peritoneal fibrosis caused by PD therapy.

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References

  1. Burkart JM. Peritoneal dialysis should be considered as the first line of renal replacement therapy for most ESRD patients. Blood Purif. 2001;19:179–84.

    Article  PubMed  CAS  Google Scholar 

  2. Chaudhary K, Sangha H, Khanna R. Peritoneal dialysis first: rationale. Clin J Am Soc Nephrol. 2011;6:447–56.

    Article  PubMed  Google Scholar 

  3. Grassmann A, Gioberge S, Moeller S, Brown G. ESRD patients in 2004: global overview of patient numbers, treatment modalities and associated trends. Nephrol Dial Transpl. 2005;20:2587–93.

    Article  Google Scholar 

  4. Bradley JA, Hamilton DN, McWhinnie DL, Briggs JD, Junor BJ. Sclerosing peritonitis after CAPD. Lancet. 1983;2:572–3.

    Article  PubMed  CAS  Google Scholar 

  5. Oreopoulos DG, Khanna R, Wu G. Sclerosing obstructive peritonitis after CAPD. Lancet. 1983;2:409.

    Article  PubMed  CAS  Google Scholar 

  6. Miyazaki M, Yuzawa Y. The role of peritoneal fibrosis in encapsulating peritoneal sclerosis. Perit Dial Int. 2005;25:S48–56.

    PubMed  Google Scholar 

  7. Mactier RA. The spectrum of peritoneal fibrosing syndromes in peritoneal dialysis. Adv Perit Dial. 2000;16:223–8.

    PubMed  CAS  Google Scholar 

  8. Yanez-Mo M, Lara-Pezzi E, Selgas R, Ramirez-Huesca M, Dominguez-Jimenez C, Jimenez-Heffernan JA, et al. Peritoneal dialysis and epithelial-to-mesenchymal transition of mesothelial cells. N Engl J Med. 2003;348:403–13.

    Article  PubMed  Google Scholar 

  9. Margetts PJ, Bonniaud P, Liu L, Hoff CM, Holmes CJ, West-Mays JA, et al. Transient overexpression of TGF-{beta}1 induces epithelial mesenchymal transition in the rodent peritoneum. J Am Soc Nephrol. 2005;16:425–36.

    Article  PubMed  CAS  Google Scholar 

  10. Devuyst O, Margetts PJ, Topley N. The pathophysiology of the peritoneal membrane. J Am Soc Nephrol. 2010;21:1077–85.

    Article  PubMed  CAS  Google Scholar 

  11. Goodlad C, Brown EA. Encapsulating peritoneal sclerosis: what have we learned? Semin Nephrol. 2011;31:183–98.

    Article  PubMed  Google Scholar 

  12. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002;13:4279–95.

    Article  PubMed  CAS  Google Scholar 

  13. Strem BM, Hicok KC, Zhu M, Wulur I, Alfonso Z, Schreiber RE, et al. Multipotential differentiation of adipose tissue-derived stem cells. Keio J Med. 2005;54:132–41.

    Article  PubMed  CAS  Google Scholar 

  14. Mitchell JB, McIntosh K, Zvonic S, Garrett S, Floyd ZE, Kloster A, et al. Immunophenotype of human adipose-derived cells: temporal changes in stromal-associated and stem cell-associated markers. Stem Cells. 2006;24:376–85.

    Article  PubMed  Google Scholar 

  15. Di Paolo N, Sacchi G. Atlas of peritoneal histology. Perit Dial Int. 2000;20:S5–96.

    PubMed  Google Scholar 

  16. Charriere G, Cousin B, Arnaud E, Andre M, Bacou F, Penicaud L, et al. Preadipocyte conversion to macrophage. Evidence of plasticity. J Biol Chem. 2003;278:9850–5.

    Article  PubMed  CAS  Google Scholar 

  17. Sonoda E, Aoki S, Uchihashi K, Soejima H, Kanaji S, Izuhara K, et al. A new organotypic culture of adipose tissue fragments maintains viable mature adipocytes for a long term, together with development of immature adipocytes and mesenchymal stem cell-like cells. Endocrinology. 2008;149:4794–8.

    Article  PubMed  CAS  Google Scholar 

  18. Sugihara H, Funatsumaru S, Yonemitsu N, Miyabara S, Toda S, Hikichi Y. A simple culture method of fat cells from mature fat tissue fragments. J Lipid Res. 1989;30:1987–95.

    PubMed  CAS  Google Scholar 

  19. Aoki S, Makino J, Nagashima A, Takezawa T, Nomoto N, Uchihashi K, et al. Fluid flow stress affects peritoneal cell kinetics: possible pathogenesis of peritoneal fibrosis. Perit Dial Int. 2011;31:466–76.

    Article  PubMed  CAS  Google Scholar 

  20. Aoki S, Ikeda S, Takezawa T, Kishi T, Makino J, Uchihashi K, et al. Prolonged effect of fluid flow stress on the proliferative activity of mesothelial cells after abrupt discontinuation of fluid streaming. Biochem Biophys Res Commun. 2011;416:391–6.

    Article  PubMed  CAS  Google Scholar 

  21. Anan M, Uchihashi K, Aoki S, Matsunobu A, Ootani A, Node K, et al. A promising culture model for analyzing the interaction between adipose tissue and cardiomyocytes. Endocrinology. 2011;152:1599–605.

    Article  PubMed  CAS  Google Scholar 

  22. Nomoto-Kojima N, Aoki S, Uchihashi K, Matsunobu A, Koike E, Ootani A, et al. Interaction between adipose tissue stromal cells and gastric cancer cells in vitro. Cell Tissue Res. 2011;344:287–98.

    Article  PubMed  CAS  Google Scholar 

  23. Aoki S, Takezawa T, Uchihashi K, Sugihara H, Toda S. Non-skin mesenchymal cell types support epidermal regeneration in a mesenchymal stem cell or myofibroblast phenotype-independent manner. Pathol Int. 2009;59:368–75.

    Article  PubMed  Google Scholar 

  24. Higashi Y, Abe K, Kuzumoto T, Hara T, Miyamoto K, Murata T, et al. Characterization of peritoneal dialysis effluent-derived cells: diagnosis of peritoneal integrity. J Artif Organs. 2012. doi:10.1007/s10047-012-0673-1.

    PubMed  Google Scholar 

  25. Kruitwagen RF, Poels LG, Willemsen WN, Jap PH, de Ronde IJ, Hanselaar TG, et al. Immunocytochemical markerprofile of endometriotic epithelial, endometrial epithelial, and mesothelial cells: a comparative study. Eur J Obstet Gynecol Reprod Biol. 1991;41:215–23.

    Article  PubMed  CAS  Google Scholar 

  26. Friedman JM. Obesity in the new millennium. Nature. 2000;404:632–4.

    PubMed  CAS  Google Scholar 

  27. Myers MG Jr. Leptin receptor signaling and the regulation of mammalian physiology. Recent Prog Horm Res. 2004;59:287–304.

    Article  PubMed  CAS  Google Scholar 

  28. Lai KN, Leung JC. Peritoneal adipocytes and their role in inflammation during peritoneal dialysis. Mediat Inflamm. 2010;2010:495416.

    Article  Google Scholar 

  29. Bradley JA, McWhinnie DL, Hamilton DN, Starnes F, Macpherson SG, Seywright M, et al. Sclerosing obstructive peritonitis after continuous ambulatory peritoneal dialysis. Lancet. 1983;2:113–4.

    Article  PubMed  CAS  Google Scholar 

  30. Dobbie JW. Pathogenesis of peritoneal fibrosing syndromes (sclerosing peritonitis) in peritoneal dialysis. Perit Dial Int. 1992;12:14–27.

    PubMed  CAS  Google Scholar 

  31. Leung JC, Chan LY, Tang SC, Chu KM, Lai KN. Leptin induces TGF-beta synthesis through functional leptin receptor expressed by human peritoneal mesothelial cell. Kidney Int. 2006;69:2078–86.

    Article  PubMed  CAS  Google Scholar 

  32. Kiyonaga H, Doi Y, Karasaki Y, Arashidani K, Itoh H, Fujimoto S. Expressions of endothelin-1, fibronectin, and interleukin-1alpha of human umbilical vein endothelial cells under prolonged culture. Med Electron Microsc. 2001;34:41–53.

    Article  PubMed  CAS  Google Scholar 

  33. Harrison DG, Cai H. Endothelial control of vasomotion and nitric oxide production. Cardiol Clin. 2003;21:289–302.

    Article  PubMed  Google Scholar 

  34. Busse R, Fleming I. Vascular endothelium and blood flow. Handb Exp Pharmacol. 2006;176(Pt 2):43–78.

    Google Scholar 

  35. Bonnefont-Rousselot D. Glucose and reactive oxygen species. Curr Opin Clin Nutr Metab Care. 2002;5:561–8.

    Article  PubMed  CAS  Google Scholar 

  36. Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res. 2000;87:840–4.

    Article  PubMed  CAS  Google Scholar 

  37. Chiu JJ, Chien S. Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives. Physiol Rev. 2011;91:327–87.

    Article  PubMed  Google Scholar 

  38. Achike FI, To NH, Wang H, Kwan CY. Obesity, metabolic syndrome, adipocytes and vascular function: a holistic viewpoint. Clin Exp Pharmacol Physiol. 2011;38:1–10.

    Article  PubMed  CAS  Google Scholar 

  39. Aoki S, Toda S, Sakemi T, Sugihara H. Coculture of endothelial cells and mature adipocytes actively promotes immature preadipocyte development in vitro. Cell Struct Funct. 2003;28:55–60.

    Article  PubMed  Google Scholar 

  40. Fernstrom A, Hylander B, Moritz A, Jacobsson H, Rossner S. Increase of intra-abdominal fat in patients treated with continuous ambulatory peritoneal dialysis. Perit Dial Int. 1998;18:166–71.

    PubMed  CAS  Google Scholar 

  41. Heimburger O. Obesity on PD patients: causes and management. Contrib Nephrol. 2003;140:91–7.

    Google Scholar 

  42. Sugihara H, Yonemitsu N, Miyabara S, Toda S. Proliferation of unilocular fat cells in the primary culture. J Lipid Res. 1987;28:1038–45.

    PubMed  CAS  Google Scholar 

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Acknowledgments

We thank H. Ideguchi, M. Nishida, F. Mutoh, S. Nakahara, and I. Nanbu for excellent technical assistance. We are grateful to Dr. T. Kishi and Dr. J. Makino for discussions and to Mr. K. Tokaichi for refining the English of the manuscript. This work was supported in part by Grants-in-Aid from the Japanese Ministry of Education, Culture, Sports, Science and Technology for Scientific Research (nos. 22590740 and 23591050 to S.T.) and by the Japan Baxter PD Fund (K.U.).

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Correspondence to Shigehisa Aoki or Shuji Toda.

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Aoki, S., Udo, K., Morimoto, H. et al. Adipose tissue behavior is distinctly regulated by neighboring cells and fluid flow stress: a possible role of adipose tissue in peritoneal fibrosis. J Artif Organs 16, 322–331 (2013). https://doi.org/10.1007/s10047-013-0702-8

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  • DOI: https://doi.org/10.1007/s10047-013-0702-8

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