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Angiogenin expression in human kidneys and W ilms' tumours: relationship with hypoxia and angiogenic factors
Author(s) -
Ramani Pramila,
Headford Alison,
SowaAvugrah Emile,
Hunt Linda P.
Publication year - 2013
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/iep.12012
Subject(s) - angiogenin , endocrinology , medicine , kidney , hypoxia (environmental) , messenger rna , vascular endothelial growth factor , angiogenesis , biology , downregulation and upregulation , lactate dehydrogenase , vascular endothelial growth factor a , chemistry , enzyme , vegf receptors , gene , biochemistry , organic chemistry , oxygen
Summary Angiogenin ( ANG ) is a potent angiogenic factor that is up‐regulated by hypoxia. ANG expression is well documented in normal tissues and in common tumours, but its expression has not been reported in the normal human kidney or in W ilms' tumours ( WT ). We examined ANG expression in WT s, human fetal kidney ( FK ) and childhood kidney ( NK ) samples and studied its relationship with microvascular density ( MVD ) and with three other hypoxia‐induced angiogenic factors: lactate dehydrogenase A ( LDHA ), vascular endothelial growth factor (VEGFA) and BHLHE40 (basic helix‐loop‐helix transcription factor E40) . Total ANG protein levels were significantly lower in WT s when compared with those in 15 matched‐paired NK s. ANG immunoreactivity was observed in the glomeruli, proximal tubules and vessels in the FK s and NK s, indicating that ANG plays a physiological role in the human kidney. ANG cellular localization and distribution in 27 WT s reflected the pattern observed in the FK s. ANG colocalized with LDHA in the perinecrotic areas of untreated WT s suggesting up‐regulation by hypoxia. There was a significant correlation between CD 31‐ MVD and ANG ‐ MVD . ANG , CD 31, VEGFA and BHLHE 40 mRNA levels were significantly lower in 15 WT s compared with matched‐paired NK s. Univariable and multivariable statistical analyses showed significant correlations between ANG and CD 31 , ANG and BHLHE 40 mRNA s and a weaker relationship between ANG and VEGFA mRNA s. ANG expression in WT s recapitulates that seen during nephrogenesis, and correlation with CD 31‐ MVD s and mRNA s is consistent with a contribution to angiogenesis in WT s. Our study contributes to the understanding of angiogenesis during development and in WT s.