Resistance to glomerulosclerosis in B6 mice disappears after menopause.
The frequency of chronic renal failure increases with age, especially in women after menopause. Glomerulosclerosis is a common cause of chronic renal failure in aging. We reported that pre-menopausal female C57BL6 (B6) mice are resistant to glomerulosclerosis, irrespective of the type of injury. However, we now show that B6 mice develop progressive glomerulosclerosis after menopause. Glomerular lesions, first recognized in 18-month-old mice, consisted of hypertrophy, vascular pole sclerosis, and mesangial cell proliferation. Diffuse but moderate mesangial sclerosis and more marked hypertrophy were present at 22 months. At 28 to 30 months the glomerulosclerosis was diffuse and increased levels of type I and type IV collagen and transforming growth factor-beta 1 mRNA were present. Urine albumin excretion was significantly increased in 30-month-old mice. Mesangial cells isolated from 28-month-old mice retained their sclerotic phenotype in vitro. Comparison of the effects of uninephrectomy (Nx) in 20-month-old and 2.5-month-old mice revealed a 1.7-fold increase in urine albumin excretion, accelerated glomerulosclerosis, and renal function insufficiency in 20-month-old Nx mice, but not in 2.5-month-old Nx mice. Glycemic levels, glucose, insulin tolerance, and blood pressure were normal at all ages. Thus, B6 mice model the increased frequency of chronic renal failure in postmenopausal women and provide a model for studying the mechanism(s) of glomerulosclerosis in aging women.
Zheng
Feng
F
Vascular Biology Institute, Department of Medicine, University of Miami School of Medicine, Miami, Florida 33136, USA. fzheng@med.miami.edu
Plati
Anna Rita
AR
Potier
Mylene
M
Schulman
Yvonne
Y
Berho
Mariana
M
Banerjee
Anita
A
Leclercq
Baudouin
B
Zisman
Ariel
A
Striker
Liliane J
LJ
Striker
Gary E
GE
D000375:Aging / Q000502:physiology*; D000419:Albuminuria / Q000473:pathology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001806:Blood Urea Nitrogen; D024042:Collagen Type I / Q000235:genetics; D024141:Collagen Type IV / Q000235:genetics; D003404:Creatinine / Q000097:blood; D004971:Estrus / Q000276:immunology*; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D007668:Kidney / Q000254:growth & development / Q000473:pathology*; D007678:Kidney Glomerulus / Q000254:growth & development / Q000473:pathology; D008593:Menopause; D051379:Mice; D008815:Mice, Inbred Strains; D014158:Transcription, Genetic
D001786:Blood Glucose; D024042:Collagen Type I; D024141:Collagen Type IV; D007328:Insulin; D003404:Creatinine