Impaired endothelial proliferation and mesenchymal transition contribute to vascular rarefaction following acute kidney injury.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901990 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1466 (Electronic) Linking ISSN: 15221466 NLM ISO Abbreviation: Am J Physiol Renal Physiol Subsets: MEDLINE
    • Publication Information:
      Original Publication: Bethesda, Md. : American Physiological Society, c1997-
    • Subject Terms:
      Cell Proliferation*; Acute Kidney Injury/*pathology ; Cell Differentiation/*physiology ; Endothelium, Vascular/*pathology ; Mesoderm/*pathology; Acute Kidney Injury/physiopathology ; Animals ; Antibodies, Anti-Idiotypic/metabolism ; Cells, Cultured ; Endothelium, Vascular/metabolism ; Female ; Male ; Mice ; Mice, Transgenic ; Models, Animal ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury/pathology ; Reperfusion Injury/physiopathology ; Vascular Endothelial Growth Factor A/physiology
    • Abstract:
      Acute kidney injury induces the loss of renal microvessels, but the fate of endothelial cells and the mechanism of potential vascular endothelial growth factor (VEGF)-mediated protection is unknown. Cumulative cell proliferation was analyzed in the kidney of Sprague-Dawley rats following ischemia-reperfusion (I/R) injury by repetitive administration of BrdU (twice daily) and colocalization in endothelial cells with CD31 or cablin. Proliferating endothelial cells were undetectable for up to 2 days following I/R and accounted for only ∼1% of BrdU-positive cells after 7 days. VEGF-121 preserved vascular loss following I/R but did not affect proliferation of endothelial, perivascular cells or tubular cells. Endothelial mesenchymal transition states were identified by localizing endothelial markers (CD31, cablin, or infused tomato lectin) with the fibroblast marker S100A4. Such structures were prominent within 6 h and sustained for at least 7 days following I/R. A Tie-2-cre transgenic crossed with a yellow fluorescent protein (YFP) reporter mouse was used to trace the fate of endothelial cells and demonstrated interstititial expansion of YFP-positive cells colocalizing with S100A4 and smooth muscle actin following I/R. The interstitial expansion of YFP cells was attenuated by VEGF-121. Multiphoton imaging of transgenic mice revealed the alteration of YFP-positive vascular cells associated with blood vessels characterized by limited perfusion in vivo. Taken together, these data indicate that vascular dropout post-AKI results from endothelial phenotypic transition combined with an impaired regenerative capacity, which may contribute to progressive chronic kidney disease.
    • References:
      Circ Res. 2007 Apr 13;100(7):1055-62. (PMID: 17347479)
      J Am Soc Nephrol. 2006 Apr;17(4):1135-42. (PMID: 16495381)
      Cardiovasc Res. 2007 Jul 1;75(1):40-50. (PMID: 17466960)
      J Clin Invest. 1989 Dec;84(6):1757-61. (PMID: 2592559)
      Am J Pathol. 2003 Dec;163(6):2289-301. (PMID: 14633603)
      Kidney Int. 2007 Jul;72(2):151-6. (PMID: 17495858)
      Blood. 2007 Mar 1;109(5):1801-9. (PMID: 17053059)
      Am J Physiol Renal Physiol. 2005 Mar;288(3):F568-77. (PMID: 15536165)
      Am J Physiol Renal Physiol. 2007 Sep;293(3):F688-95. (PMID: 17626153)
      Am J Pathol. 2008 Dec;173(6):1617-27. (PMID: 19008372)
      Kidney Int. 2001 Oct;60(4):1297-308. (PMID: 11576344)
      FASEB J. 1999 Jan;13(1):9-22. (PMID: 9872925)
      Am J Physiol Renal Physiol. 2003 Feb;284(2):F338-48. (PMID: 12388385)
      Am J Kidney Dis. 2001 Mar;37(3):601-11. (PMID: 11228186)
      J Am Soc Nephrol. 2008 Dec;19(12):2282-7. (PMID: 18987304)
      Am J Kidney Dis. 2010 Jul;56(1):122-31. (PMID: 20346560)
      J Clin Invest. 2005 Jul;115(7):1756-64. (PMID: 16007252)
      J Cereb Blood Flow Metab. 2004 Feb;24(2):237-44. (PMID: 14747750)
      Circulation. 2003 Jul 8;108(1):97-103. (PMID: 12821549)
      J Pharmacol Exp Ther. 2003 Mar;304(3):905-12. (PMID: 12604664)
      J Am Soc Nephrol. 2007 Jan;18(1):165-75. (PMID: 17135399)
      Br J Cancer. 2004 Jan 12;90(1):253-62. (PMID: 14710237)
      Kidney Int. 1997 Nov;52(5):1169-79. (PMID: 9350640)
      Am J Physiol Renal Physiol. 2008 Apr;294(4):F928-36. (PMID: 18272597)
      Am J Physiol Renal Physiol. 2000 Jul;279(1):F3-F11. (PMID: 10894783)
      Kidney Int. 2001 May;59(5):1850-8. (PMID: 11318956)
      J Clin Invest. 1999 Oct;104(7):913-23. (PMID: 10510332)
      Am J Physiol Renal Physiol. 2006 Dec;291(6):F1248-54. (PMID: 16804104)
      Am J Physiol Regul Integr Comp Physiol. 2009 Nov;297(5):R1358-63. (PMID: 19710386)
      Exp Hematol. 2004 Dec;32(12):1226-37. (PMID: 15588947)
      Kidney Int. 2006 Jan;69(1):184-9. (PMID: 16374442)
      Am J Physiol Renal Physiol. 2008 Dec;295(6):F1648-57. (PMID: 18799550)
      Am J Pathol. 1998 Aug;153(2):381-94. (PMID: 9708799)
      J Am Soc Nephrol. 2006 Nov;17(11):2992-8. (PMID: 17035610)
      Am J Physiol Renal Physiol. 2003 Apr;284(4):F608-27. (PMID: 12620919)
      Am J Physiol Renal Physiol. 2007 Jul;293(1):F269-78. (PMID: 17507599)
      Am J Physiol Heart Circ Physiol. 2007 Jan;292(1):H285-94. (PMID: 16963618)
      Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11876-80. (PMID: 1465411)
      J Clin Invest. 2002 Aug;110(3):341-50. (PMID: 12163453)
      Am J Physiol Renal Physiol. 2001 Nov;281(5):F887-99. (PMID: 11592947)
      Am J Kidney Dis. 2009 Jun;53(6):961-73. (PMID: 19346042)
      Kidney Int. 2009 Jun;75(11):1145-1152. (PMID: 19340094)
      J Am Soc Nephrol. 2009 Jan;20(1):223-8. (PMID: 19020007)
      Am J Physiol. 1999 Nov;277(5):H1985-96. (PMID: 10564155)
      Kidney Int. 2000 Jan;57(1):307-13. (PMID: 10620213)
      Am J Physiol Renal Physiol. 2008 Jun;294(6):F1265-72. (PMID: 18287400)
    • Grant Information:
      R01 DK069408 United States DK NIDDK NIH HHS; R01 DK063114 United States DK NIDDK NIH HHS; P30-DK-79312 United States DK NIDDK NIH HHS; R01 DK077124-03S1 United States DK NIDDK NIH HHS; DK-069408 United States DK NIDDK NIH HHS; DK-063114 United States DK NIDDK NIH HHS; R01 DK077124-04 United States DK NIDDK NIH HHS; R01 DK077124 United States DK NIDDK NIH HHS; DK-77124 United States DK NIDDK NIH HHS; DK-79312 United States DK NIDDK NIH HHS
    • Accession Number:
      0 (Antibodies, Anti-Idiotypic)
      0 (Platelet Endothelial Cell Adhesion Molecule-1)
      0 (Vascular Endothelial Growth Factor A)
      0 (vascular endothelial growth factor A, mouse)
      0 (vascular endothelial growth factor A, rat)
    • Publication Date:
      Date Created: 20101203 Date Completed: 20110420 Latest Revision: 20230528
    • Publication Date:
      20230528
    • Accession Number:
      PMC3064142
    • Accession Number:
      10.1152/ajprenal.00546.2010
    • Accession Number:
      21123492