title: Synthetic/secreting and apoptotic phenotypes in renal biopsy tissues from hypertensive nephrosclerosis patients.
abstract: The major glomerular abnormalities in hypertensive nephrosclerosis are described as glomerular obsolescence (GO), glomerulosclerosis (GS), and glomerular collapse (GC). However, glomerular cellular changes caused by hypertensive insults have not been well analyzed. Using an immunoenzyme method, we examined eleven biopsy samples from patients with hypertensive nephrosclerosis for two synthetic and secreting phenotypes, a-smooth muscle actin (alpha-SMA) and collagen type III (Col. III), and two apoptotic phenotypes, pro-apoptotic molecule Bax and anti-apoptotic molecule BcI-2. Together with the glomerular and vascular changes and interstitial fibrosis (IF) area, the results were scored quantitatively and semi-quantitatively and compared to the clinical findings, which included systolic blood pressure (SBP), mean arterial pressure (MAP), serum creatinine levels (sCr) and creatinine clearance (Ccr), using univariate and multivariate analyses. As a result, GS was frequently observed in the mild-to-moderate hypertensive group (140 < or = SBP<180 mmHg), whereas GC was positively correlated with SBP. Furthermore, there was a positive correlation of GS with mesangial alpha-SMA and Col. III, suggesting that GS was the reflection of these synthetic and secreting phenotypic changes in mesangial cells. Endothelial Bax was positively correlated with Ccr (p<0.01); in contrast, podocytic Bax was positively correlated with sCr (p<0.05) and showed a tendency to correlate with MAP (p=0.054). In conclusion, these findings support the view that mesangial synthetic and secreting phenotypic changes may be a reflection of cellular activation caused by mild-to-moderate hypertension and that apoptotic phenotypic expression in podocytes, rather than endothelial cells, may be related to the development of a severe form of hypertensive nephrosclerosis.
authors.affiliation: Division of Nephrology, University of Fukui Hospital, Fukui, Japan.
authors.forename: Noriyo
authors.initials: N
authors.lastname: Kimura
authors.forename: Satomi
authors.initials: S
authors.lastname: Yonemoto
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Machiguchi
authors.forename: Xuan
authors.initials: X
authors.lastname: Li
authors.forename: Hideki
authors.initials: H
authors.lastname: Kimura
authors.forename: Haruyoshi
authors.initials: H
authors.lastname: Yoshida
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D005260:Female; D006801:Humans; D006973:Hypertension / Q000473:pathology* / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009400:Nephrosclerosis / Q000473:pathology* / Q000503:physiopathology; D010641:Phenotype; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000199:Actins; D015415:Biomarkers; D024061:Collagen Type III; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein