Resistance to glomerulosclerosis in B6 mice disappears after menopause

Feng Zheng, Anna Rita Plati, Mylene Potier, Yvonne Schulman, Mariana Berho, Anita Banerjee, Baudouin Leclercq, Ariel Zisman, Liliane J. Striker, Gary E. Striker

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57 Scopus citations

Abstract

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-β 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.

Original languageEnglish (US)
Pages (from-to)1339-1348
Number of pages10
JournalAmerican Journal of Pathology
Volume162
Issue number4
DOIs
StatePublished - Apr 1 2003

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Zheng, F., Plati, A. R., Potier, M., Schulman, Y., Berho, M., Banerjee, A., Leclercq, B., Zisman, A., Striker, L. J., & Striker, G. E. (2003). Resistance to glomerulosclerosis in B6 mice disappears after menopause. American Journal of Pathology, 162(4), 1339-1348. https://doi.org/10.1016/S0002-9440(10)63929-6