title: Implication of peritubular capillary loss and altered expression of vascular endothelial growth factor in IgA nephropathy.
abstract: OBJECTIVE
  To determine the roles of peritubular capillary (PTC) loss and expression of vascular endothelial growth factor (VEGF) and its transcription factor, hypoxia-inducible factor-1 (HIF-1), in the progression of IgA nephropathy (IgAN), we analyzed the expression of VEGF and HIF-1, and the number of PTCs in patients with variable severity of IgAN.
  
  
  METHODS
  Renal biopsy specimens from patients with IgAN (n = 23) were classified according to interstitial injury score: grade 0 (0%), grade 1 (1-25%), grade 2 (25-50%) and grade 3 (50-100%). We examined the immunohistochemical expression of CD34, VEGF and HIF-1alpha.
  
  
  RESULTS
  VEGF was expressed in the cytoplasm of tubular epithelia, and VEGF-positive area significantly expanded in grades 1 (35.5 +/- 5.9%, mean +/- SD) and 2 (32.5 +/- 5.9%) compared with grade 0 (23.4 +/- 4.5%). The numbers of PTCs were significantly lower in grades 2 (559 +/- 49/mm2) and 3 (510 +/- 56/mm2) than grade 0 (708 +/- 49/mm2). HIF-1alpha was weakly expressed in tubular epithelia in grade 0, increased with progression to grade 2, and markedly decreased in grade 3. It was also increased in pericapsular interstitial area in grade 1. The expression pattern of HIF-1alpha did not parallel that of VEGF. In renal biopsies of 5 control patients with minor glomerular abnormality, glomerular expression levels of VEGF and HIF-1alpha were similar to those of IgAN grade 0 kidneys.
  
  
  CONCLUSIONS
  VEGF production was accelerated in the early stage of IgAN but it did not protect against PTC injury/loss. The lack of correlation between VEGF and HIF-1alpha expression suggests HIF-independent VEGF production in IgAN.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan.
authors.forename: Tamehachi
authors.initials: T
authors.lastname: Namikoshi
authors.forename: Minoru
authors.initials: M
authors.lastname: Satoh
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Horike
authors.forename: Sohachi
authors.initials: S
authors.lastname: Fujimoto
authors.forename: Sayaka
authors.initials: S
authors.lastname: Arakawa
authors.forename: Tamaki
authors.initials: T
authors.lastname: Sasaki
authors.forename: Naoki
authors.initials: N
authors.lastname: Kashihara
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D001706:Biopsy; D002196:Capillaries / Q000378:metabolism / Q000473:pathology; D005260:Female; D005922:Glomerulonephritis, IGA / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007150:Immunohistochemistry; D007684:Kidney Tubules / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012079:Renal Circulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A