Our preliminary data suggests that mesangial cell precursors are derived from the bone marrow. The purpose of this proposal is to determine if the mesangial sclerosis that characterizes accelerated aging originates in bone marrow precursors. A gradual loss in renal function during aging is not inevitable. It occurs in those elderly individuals who are sclerosis-prone and who have intercurrent diseases such as hypertension or diabetes. Thus, there are two aging populations, one that may develop renal disease (sclerosis-prone) and one that does not (sclerosis-resistant). We developed strains of sclerosis-resistant (C57) and sclerosis-prone (ROP) mice that model these two populations. Kidney lesions were mild or absent in aging C57 mice. Aging ROP mice had modest glomeruloscierosis, in the absence of an injury, but the process was sharply accelerated, and occurred at an earlier age with a reduced nephron number (due to the Os gene) or diabetes mellitus. We propose that the glomeruloscierosis found in sclerosis-prone mice with reduced renal mass (ROP Os/+) mice could be used as a model of accelerated aging. The glomeruloscierosis in ROP Os/+ mice was restricted to the mesangial regions and was characterized by a stable mesangial cell phenotypic changes. We hypothesize that the phenotypic changes arise in the bone marrow. We propose to confirm the bone marrow origin of mesangial cell progenitors and to determine if the site of the phenotypic change induced by rapid aging in sclerosis-prone mice is in the marrow or the kidney. We will determine if mesangial cell progenitors can be isolated from the bone marrow and/or the circulation. We will also assess the effect(s) of donor and recipient age on the number and ability of mesangial precursors to repopulate and induce/reduce glomerular lesions. Finally, we will examine the gene expression pattern of the phenotypic changes in mesangial cells by DNA microarrays.

National Institute of Health (NIH)
National Institute on Aging (NIA)
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General Medicine B Study Section (GMB)
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Bellino, Francis
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University of Miami School of Medicine
Internal Medicine/Medicine
Schools of Medicine
United States
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