DOI QR코드

DOI QR Code

Intra-renal slow cell-cycle cells contribute to the restoration of kidney tubules injured by ischemia/reperfusion

  • Kim, Jin-U (Department of Anatomy, Kyungpook National University School of Medicine) ;
  • Kim, Jee-In (Department of Anatomy, Kyungpook National University School of Medicine) ;
  • Na, Yeon-Kyung (Department of Nursing, College of Nursing, Kyungpook National University) ;
  • Park, Kwon-Moo (Department of Anatomy, Kyungpook National University School of Medicine)
  • Published : 2011.09.30

Abstract

Renal epithelial cells damaged by ischemia/reperfusion (I/R) can be restored by timely and appropriate treatment. Recent studies have reported that intra renal adult kidney stem cells contribute to the restoration of tubules damaged by I/R. Here, we determined the role of adult tubular cells in the restoration of damaged tubules. We labeled slow cell-cycle cells (SCCs) with 5-bromo-2'-deoxyuridine (BrdU) and investigated their location in the kidneys as well as their contribution to the restoration of tubular cells damaged by I/R injury in mice. Thirty minutes of bilateral ischemia resulted in severe disruption of tubular epithelial cells along with a decline in renal function. The post-ischemic disruption of tubular epithelial cells was most severe in the S3 segment of the outer stripe of the outer medulla. Damaged tubules demonstrated gradual recovery of renal function over time. BrdU-labeled SCCs were mainly observed in tubules located at the junction of cortex and outer medulla, as well as in the inner medulla. The tubular SCCs expressed functional tubule cell markers such as Na/K-ATPase, Na-K-Cl cotransporter-2, and aquaporin 1 and 2. BrdU-labeled SCCs survived I/R injury and proliferated. These results demonstrate that SCCs present in tubules contribute to the restoration of tubular epithelial cells injured by I/R.

Keywords

References

  1. Lange C, Togel F, Ittrich H, Clayton F, Nolte-Ernsting C, Zander AR, Westenfelder C. Administered mesenchymal stem cells enhance recovery from ischemia/reperfusion-induced acute renal failure in rats. Kidney Int 2005;68:1613-7. https://doi.org/10.1111/j.1523-1755.2005.00573.x
  2. Thadhani R, Pascual M, Bonventre JV. Acute renal failure. N Engl J Med 1996;334:1448-60. https://doi.org/10.1056/NEJM199605303342207
  3. Brodie JC, Humes HD. Stem cell approaches for the treatment of renal failure. Pharmacol Rev 2005;57:299-313. https://doi.org/10.1124/pr.57.3.3
  4. Duffield JS, Park KM, Hsiao LL, Kelley VR, Scadden DT, Ichimura T, Bonventre JV. Restoration of tubular epithelial cells during repair of the postischemic kidney occurs independently of bone marrow-derived stem cells. J Clin Invest 2005;115:1743-55. https://doi.org/10.1172/JCI22593
  5. Witzgall R, Brown D, Schwarz C, Bonventre JV. Localization of proliferating cell nuclear antigen, vimentin, c-Fos, and clusterin in the postischemic kidney. Evidence for a heterogenous genetic response among nephron segments, and a large pool of mitotically active and dedifferentiated cells. J Clin Invest 1994;93:2175-88. https://doi.org/10.1172/JCI117214
  6. Gupta S, Verfaillie C, Chmielewski D, Kim Y, Rosenberg ME. A role for extrarenal cells in the regeneration following acute renal failure. Kidney Int 2002;62:1285-90. https://doi.org/10.1111/j.1523-1755.2002.kid569.x
  7. Kale S, Karihaloo A, Clark PR, Kashgarian M, Krause DS, Cantley LG. Bone marrow stem cells contribute to repair of the ischemically injured renal tubule. J Clin Invest 2003;112:42-9. https://doi.org/10.1172/JCI17856
  8. Lin F, Cordes K, Li L, Hood L, Couser WG, Shankland SJ, Igarashi P. Hematopoietic stem cells contribute to the regeneration of renal tubules after renal ischemia-reperfusion injury in mice. J Am Soc Nephrol 2003;14:1188-99. https://doi.org/10.1097/01.ASN.0000061595.28546.A0
  9. Poulsom R, Forbes SJ, Hodivala-Dilke K, Ryan E, Wyles S, Navaratnarasah S, Jeffery R, Hunt T, Alison M, Cook T, Pusey C, Wright NA. Bone marrow contributes to renal parenchymal turnover and regeneration. J Pathol 2001;195:229-35. https://doi.org/10.1002/path.976
  10. Bonventre JV. Dedifferentiation and proliferation of surviving epithelial cells in acute renal failure. J Am Soc Nephrol 2003;14 Suppl 1:S55-61. https://doi.org/10.1097/01.ASN.0000067652.51441.21
  11. Lin F, Moran A, Igarashi P. Intrarenal cells, not bone marrowderived cells, are the major source for regeneration in postischemic kidney. J Clin Invest 2005;115:1756-64. https://doi.org/10.1172/JCI23015
  12. Kim J, Park KM. Locations of slow-cycling cells, adult stem cells, in the organs of adult mouse. Korean J Anat 2007;40:347-57.
  13. Kim K, Lee KM, Han DJ, Yu E, Cho YM. Adult stem cell-like tubular cells reside in the corticomedullary junction of the kidney. Int J Clin Exp Pathol 2008;1:232-41.
  14. Kim K, Park BH, Ihm H, Kim KM, Jeong J, Chang JW, Cho YM. Expression of stem cell marker CD133 in fetal and adult human kidneys and pauci-immune crescentic glomerulonephritis. Histol Histopathol 2011;26:223-32.
  15. Oliver JA, Maarouf O, Cheema FH, Martens TP, Al-Awqati Q. The renal papilla is a niche for adult kidney stem cells. J Clin Invest 2004;114:795-804. https://doi.org/10.1172/JCI20921
  16. Lavker RM, Sun TT. Epidermal stem cells: properties, markers, and location. Proc Natl Acad Sci U S A 2000;97:13473-5. https://doi.org/10.1073/pnas.250380097
  17. Kim J, Kim JI, Kwon TH, Park KM. Kidney tubular cell regeneration starts in the deep cortex after ischemia. Korean J Nephrol 2008;27:536-44.
  18. Park KM, Chen A, Bonventre JV. Prevention of kidney ischemia/reperfusion-induced functional injury and JNK, p38, and MAPK kinase activation by remote ischemic pretreatment. J Biol Chem 2001;276:11870-6. https://doi.org/10.1074/jbc.M007518200
  19. Park KM, Kramers C, Vayssier-Taussat M, Chen A, Bonventre JV. Prevention of kidney ischemia/reperfusion-induced functional injury, MAPK and MAPK kinase activation, and inflammation by remote transient ureteral obstruction. J Biol Chem 2002;277:2040-9. https://doi.org/10.1074/jbc.M107525200
  20. Bussolati B, Bruno S, Grange C, Buttiglieri S, Deregibus MC, Cantino D, Camussi G. Isolation of renal progenitor cells from adult human kidney. Am J Pathol 2005;166:545-55. https://doi.org/10.1016/S0002-9440(10)62276-6
  21. Humphreys BD, Valerius MT, Kobayashi A, Mugford JW, Soeung S, Duffield JS, McMahon AP, Bonventre JV. Intrinsic epithelial cells repair the kidney after injury. Cell Stem Cell 2008;2:284-91. https://doi.org/10.1016/j.stem.2008.01.014
  22. Loverre A, Capobianco C, Ditonno P, Battaglia M, Grandaliano G, Schena FP. Increase of proliferating renal progenitor cells in acute tubular necrosis underlying delayed graft function. Transplantation 2008;85:1112-9. https://doi.org/10.1097/TP.0b013e31816a8891
  23. Fujigaki Y, Goto T, Sakakima M, Fukasawa H, Miyaji T, Yamamoto T, Hishida A. Kinetics and characterization of initially regenerating proximal tubules in S3 segment in response to various degrees of acute tubular injury. Nephrol Dial Transplant 2006;21:41-50. https://doi.org/10.1093/ndt/gfi035
  24. Fujigaki Y, Sakakima M, Sun Y, Fujikura T, Tsuji T, Yasuda H, Hishida A. Cell division and phenotypic regression of proximal tubular cells in response to uranyl acetate insult in rats. Nephrol Dial Transplant 2009;24:2686-92. https://doi.org/10.1093/ndt/gfp199
  25. Sakakima M, Fujigaki Y, Yamamoto T, Hishida A. A distinct population of tubular cells in the distal S3 segment contributes to S3 segment regeneration in rats following acute renal failure induced by uranyl acetate. Nephron Exp Nephrol 2008;109:e57-70. https://doi.org/10.1159/000142100
  26. Maeshima A, Yamashita S, Nojima Y. Identification of renal progenitor-like tubular cells that participate in the regeneration processes of the kidney. J Am Soc Nephrol 2003;14:3138-46. https://doi.org/10.1097/01.ASN.0000098685.43700.28

Cited by

  1. Donor ABCB1 Variant Associates with Increased Risk for Kidney Allograft Failure vol.23, pp.11, 2011, https://doi.org/10.1681/asn.2012030260
  2. The Evolving Landscape of Neurotoxicity by Unconjugated Bilirubin: Role of Glial Cells and Inflammation vol.3, pp.None, 2011, https://doi.org/10.3389/fphar.2012.00088
  3. Stem Cells and Their Role in Renal Ischaemia Reperfusion Injury vol.37, pp.1, 2011, https://doi.org/10.1159/000345731
  4. Reduction of oxidative stress during recovery accelerates normalization of primary cilia length that is altered after ischemic injury in murine kidneys vol.304, pp.10, 2011, https://doi.org/10.1152/ajprenal.00427.2012
  5. Recruitment and subsequent proliferation of bone marrow-derived cells in the postischemic kidney are important to the progression of fibrosis vol.306, pp.12, 2011, https://doi.org/10.1152/ajprenal.00017.2014
  6. Distinct populations of label-retaining cells in the adult kidney are defined temporally and exhibit divergent regional distributions vol.307, pp.11, 2011, https://doi.org/10.1152/ajprenal.00213.2014
  7. Hydrogen sulfide accelerates the recovery of kidney tubules after renal ischemia/reperfusion injury vol.30, pp.9, 2011, https://doi.org/10.1093/ndt/gfv226
  8. The role of long-term label-retaining cells in the regeneration of adult mouse kidney after ischemia/reperfusion injury vol.7, pp.1, 2011, https://doi.org/10.1186/s13287-016-0324-1
  9. Adipose tissue derived mesenchymal stem cell transplantation in the treatment of ischemia/reperfusion induced acute kidney injury in rats. Application route and therapeutic window vol.33, pp.11, 2011, https://doi.org/10.1590/s0102-865020180110000008
  10. Effects of Ginkgo Biloba Extract on H9C2 microRNA-1, BCL-2 and Caspase Pathways in Cardiomyocytes vol.9, pp.7, 2011, https://doi.org/10.12677/acm.2019.97130
  11. Cyclosporin A aggravates hydrogen peroxide-induced cell death in kidney proximal tubule epithelial cells vol.52, pp.3, 2011, https://doi.org/10.5115/acb.18.192
  12. Kidney Cells Regeneration: Dedifferentiation of Tubular Epithelium, Resident Stem Cells and Possible Niches for Renal Progenitors vol.20, pp.24, 2011, https://doi.org/10.3390/ijms20246326