Increased renal angiopoietin-1 expression in folic acid-induced nephrotoxicity in mice

D. A. Long, A. S. Woolf, T. Suda, H. T. Yuan

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Growth factors affect epithelial regeneration after acute renal injury, but less is known regarding the expression of vascular growth factors in this setting. A mouse model of folic acid (FA)-induced nephrotoxicity was used to study the expression of angiopoietins (Ang), factors that bind the Tie-2 receptor and modulate endothelial growth. Tubular damage was detected 1 d after FA administration; in the next 14 d, most tubules regenerated but patchy atrophy, with interstitial fibrosis, was also observed. Ang-1 immunostaining was detected between cortical tubules and in the vasa rectae of vehicle-treated animals. FA-induced nephropathy was associated with the acquisition of Ang-1 immunostaining in renal arterial walls and in a subset of injured cortical tubules that failed to stain with periodic acid-Schiff stain, which indicated that they were distal tubules. Renal Ang-1 protein levels were significantly increased after FA administration, compared with time-matched control values, as assessed by Western blotting. Capillaries between regenerating tubules expressed both Tie-2 and platelet-endothelial cell adhesion molecule. A subset of these endothelia expressed proliferating cell nuclear antigen, whereas capillary proliferation was absent in control samples. Therefore, FA-induced nephropathy is associated with increased Ang-1 protein expression in renal epithelia and arteries. In addition, Tie-2-expressing capillaries near damaged cortical tubules undergo proliferation. Further experiments are required to establish whether these events are functionally related.

Original languageEnglish
Pages (from-to)2721-2731
Number of pages11
JournalJournal of the American Society of Nephrology
Volume12
Issue number12
Publication statusPublished - 2001

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Angiopoietin-1
Folic Acid
Kidney
Intercellular Signaling Peptides and Proteins
Coloring Agents
Angiopoietins
Periodic Acid
Proliferating Cell Nuclear Antigen
Cell Adhesion Molecules
Renal Artery
Acute Kidney Injury
Atrophy
Endothelium
Regeneration
Proteins
Fibrosis
Blood Platelets
Epithelium
Endothelial Cells
Western Blotting

ASJC Scopus subject areas

  • Nephrology

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Increased renal angiopoietin-1 expression in folic acid-induced nephrotoxicity in mice. / Long, D. A.; Woolf, A. S.; Suda, T.; Yuan, H. T.

In: Journal of the American Society of Nephrology, Vol. 12, No. 12, 2001, p. 2721-2731.

Research output: Contribution to journalArticle

Long, D. A. ; Woolf, A. S. ; Suda, T. ; Yuan, H. T. / Increased renal angiopoietin-1 expression in folic acid-induced nephrotoxicity in mice. In: Journal of the American Society of Nephrology. 2001 ; Vol. 12, No. 12. pp. 2721-2731.
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