Advanced Glomerulosclerosis Is Reversible in Nephrotic Mice

• Published in: Biochemical and biophysical research communications 2001-06, Vol.284 (3), p.707-713
• Main Authors: Mizuno-Horikawa, Yoko, Mizuno, Shinya, Tamura, Shinichi, Kurosawa, Tsutomu
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Fibroblasts; Fibronectins - metabolism; glomerular hypertrophy; glomerular remodeling; glomerulosclerosis; Glomerulosclerosis, Focal Segmental - metabolism; Glomerulosclerosis, Focal Segmental - pathology; Glomerulosclerosis, Focal Segmental - therapy; Hypertrophy - pathology; Hypertrophy - therapy; Kidney Failure, Chronic - metabolism; Kidney Failure, Chronic - pathology; Kidney Failure, Chronic - therapy; Kidney Glomerulus - cytology; Kidney Glomerulus - metabolism; Kidney Glomerulus - pathology; Ligation; Mice; Mice, Mutant Strains; mouse model; myofibroblasts; nephrotic syndrome; Sclerosis; Ureter; ureter ligation
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2001.4903

Advanced glomerulosclerosis, a common hallmark of chronic renal diseases (CRD) is believed to be irreversible, and it is thought that glomerular hyperfiltration and hypertrophy may participate in its pathogenesis. We demonstrate here that glomerulosclerosis is “reversible” in an animal model. We used nephrotic ICGN (nep/nep) mice which showed a rapid progression of glomerulosclerosis, accompanied by histological findings for glomerular hyperfiltration. It is known that ureter ligation reduces glomerular filtration in ligated kidneys. When ureter ligation was applied to our model, glomerulosclerosis (characterized by myofibroblast hyperplasia and over-accumulated matrix protein) weakened in conjunction with suppressed glomerular hypertrophy. During this process, glomerular myofibroblasts showed apoptotic cell death after unilateral ureter ligation (UUO) treatment. Our results suggest that inhibition of glomerular filtration in sclerotic tufts may cause glomerular remodeling through the modulation of molecular and cellular sclerogenesis.