TUDCA-treated Chronic Kidney Disease-derived HMSCs Improve Therapeutic Efficacy in Ischemic Disease Via PrP

Overview

Journal Redox Biol

Specialties Biology
Cell Biology
Endocrinology

Date 2019 Feb 21

PMID 30785084

Citations 10

Authors

Yeo Min Yoon

SangMin Kim

Yong-Seok Han

Chul Won Yun

Jun Hee Lee

Hyunjin Noh

Sang Hun Lee

Affiliations

Soon will be listed here.

Abstract

Although autologous human mesenchymal stem cells (hMSCs) are a promising source for regenerative stem cell therapy in chronic kidney disease (CKD), the barriers associated with pathophysiological conditions limit therapeutic applicability to patients. We confirmed that level of cellular prion protein (PrP) in serum was decreased and mitochondria function of CKD-derived hMSCs (CKD-hMSCs) was impaired in patients with CKD. We proved that treatment of CKD-hMSCs with tauroursodeoxycholic acid (TUDCA), a bile acid, enhanced the mitochondrial function of these cells through regulation of PINK1-PrP-dependent pathway. In a murine hindlimb ischemia model with CKD, tail vein injection of TUDCA-treated CKD-hMSCs improved the functional recovery, including kidney recovery, limb salvage, blood perfusion ratio, and vessel formation along with restored expression of PrP in the blood serum of the mice. These data suggest that TUDCA-treated CKD-hMSCs are a promising new autologous stem cell therapeutic intervention that dually treats cardiovascular problems and CKD in patients.

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References

Miele G, Jeffrey M, Turnbull D, Manson J, Clinton M . Ablation of cellular prion protein expression affects mitochondrial numbers and morphology. Biochem Biophys Res Commun. 2002; 291(2):372-7. DOI: 10.1006/bbrc.2002.6460. View

Sarnak M, Levey A, Schoolwerth A, Coresh J, Culleton B, Hamm L . Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and.... Hypertension. 2003; 42(5):1050-65. DOI: 10.1161/01.HYP.0000102971.85504.7c. View

Little M . Regrow or repair: potential regenerative therapies for the kidney. J Am Soc Nephrol. 2006; 17(9):2390-401. DOI: 10.1681/ASN.2006030218. View

Faris R, Moore R, Ward A, Race B, Dorward D, Hollister J . Cellular prion protein is present in mitochondria of healthy mice. Sci Rep. 2017; 7:41556. PMC: 5288712. DOI: 10.1038/srep41556. View

Hornshaw M, McDermott J, Candy J, Lakey J . Copper binding to the N-terminal tandem repeat region of mammalian and avian prion protein: structural studies using synthetic peptides. Biochem Biophys Res Commun. 1995; 214(3):993-9. DOI: 10.1006/bbrc.1995.2384. View

DHooge R, Van de Vijver G, van Bogaert P, Marescau B, Vanholder R, De Deyn P . Involvement of voltage- and ligand-gated Ca2+ channels in the neuroexcitatory and synergistic effects of putative uremic neurotoxins. Kidney Int. 2003; 63(5):1764-75. DOI: 10.1046/j.1523-1755.2003.00912.x. View

Pinheiro L, Linden R, Mariante R . Activation and function of murine primary microglia in the absence of the prion protein. J Neuroimmunol. 2015; 286:25-32. DOI: 10.1016/j.jneuroim.2015.07.002. View

Schlieper G, Schurgers L, Brandenburg V, Reutelingsperger C, Floege J . Vascular calcification in chronic kidney disease: an update. Nephrol Dial Transplant. 2015; 31(1):31-9. DOI: 10.1093/ndt/gfv111. View

Liang X, Ding Y, Zhang Y, Tse H, Lian Q . Paracrine mechanisms of mesenchymal stem cell-based therapy: current status and perspectives. Cell Transplant. 2013; 23(9):1045-59. DOI: 10.3727/096368913X667709. View

10.

Lee J, Ryu J, Han Y, Zia M, Kwon H, Noh H . Fucoidan improves bioactivity and vasculogenic potential of mesenchymal stem cells in murine hind limb ischemia associated with chronic kidney disease. J Mol Cell Cardiol. 2016; 97:169-79. DOI: 10.1016/j.yjmcc.2016.05.011. View

11.

Lazarou M, Jin S, Kane L, Youle R . Role of PINK1 binding to the TOM complex and alternate intracellular membranes in recruitment and activation of the E3 ligase Parkin. Dev Cell. 2012; 22(2):320-33. PMC: 3288275. DOI: 10.1016/j.devcel.2011.12.014. View

12.

Prusiner S . Novel proteinaceous infectious particles cause scrapie. Science. 1982; 216(4542):136-44. DOI: 10.1126/science.6801762. View

13.

Zhan M, Brooks C, Liu F, Sun L, Dong Z . Mitochondrial dynamics: regulatory mechanisms and emerging role in renal pathophysiology. Kidney Int. 2013; 83(4):568-81. PMC: 3612360. DOI: 10.1038/ki.2012.441. View

14.

Martin-Lanneree S, Halliez S, Hirsch T, Hernandez-Rapp J, Passet B, Tomkiewicz C . The Cellular Prion Protein Controls Notch Signaling in Neural Stem/Progenitor Cells. Stem Cells. 2016; 35(3):754-765. DOI: 10.1002/stem.2501. View

15.

Castro A, Coresh J . CKD surveillance using laboratory data from the population-based National Health and Nutrition Examination Survey (NHANES). Am J Kidney Dis. 2009; 53(3 Suppl 3):S46-55. PMC: 2677815. DOI: 10.1053/j.ajkd.2008.07.054. View

16.

Haddon D, Hughes M, Antignano F, Westaway D, Cashman N, McNagny K . Prion protein expression and release by mast cells after activation. J Infect Dis. 2009; 200(5):827-31. DOI: 10.1086/605022. View

17.

Sola S, Brito M, Brites D, Moura J, Rodrigues C . Membrane structural changes support the involvement of mitochondria in the bile salt-induced apoptosis of rat hepatocytes. Clin Sci (Lond). 2002; 103(5):475-85. DOI: 10.1042/cs1030475. View

18.

Lin W, Zhang Q, Liu L, Yin S, Liu Z, Cao W . Klotho restoration via acetylation of Peroxisome Proliferation-Activated Receptor γ reduces the progression of chronic kidney disease. Kidney Int. 2017; 92(3):669-679. DOI: 10.1016/j.kint.2017.02.023. View

19.

Gabriele S, Sacco R, Altieri L, Neri C, Urbani A, Bravaccio C . Slow intestinal transit contributes to elevate urinary p-cresol level in Italian autistic children. Autism Res. 2015; 9(7):752-9. DOI: 10.1002/aur.1571. View

20.

Yoon Y, Lee J, Yun S, Han Y, Yun C, Lee H . Tauroursodeoxycholic acid reduces ER stress by regulating of Akt-dependent cellular prion protein. Sci Rep. 2016; 6:39838. PMC: 5177936. DOI: 10.1038/srep39838. View