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Glomerulosclerosis is transmitted by bone marrow–derived mesangial cell progenitors
Flavia Cornacchia, … , Liliane J. Striker, Gary E. Striker
Flavia Cornacchia, … , Liliane J. Striker, Gary E. Striker
Published December 1, 2001
Citation Information: J Clin Invest. 2001;108(11):1649-1656. https://doi.org/10.1172/JCI12916.
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Article

Glomerulosclerosis is transmitted by bone marrow–derived mesangial cell progenitors

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Abstract

We found that ROP Os/+ (Os/+) mice had diffuse glomerulosclerosis and glomerular hypertrophy and that their mesangial cells (the vascular smooth muscle cells of the glomerulus) displayed an apparent sclerosing phenotype. Since mesangial cells are the major source of scar tissue in glomerulosclerosis, we postulated that the sclerosis phenotype was carried by mesangial cell progenitors and that this phenotype could be derived from the bone marrow (BM). Therefore, we transplanted BM from Os/+ mice into congenic ROP +/+ mice (+/+ mice), which have normal glomeruli. We found that glomeruli of +/+ recipients of Os/+ marrow contained the Os/+ genotype, were hypertrophied, and contained increased extracellular matrix. Clones of recipient glomerular mesangial cells with the donor genotype were found in all +/+ recipients that developed mesangial sclerosis and glomerular hypertrophy, whereas +/+ recipients of +/+ BM had normal glomeruli. Thus, the sclerotic (Os/+) or normal (+/+) genotype and phenotype were present in, and transmitted by, BM-derived progenitors. These data show that glomerular mesangial cell progenitors are derived from the BM and can deliver a disease phenotype to normal glomeruli. Glomerular lesions may therefore be perpetuated or aggravated, rather than resolved, by newly arriving progenitor cells exhibiting a disease phenotype.

Authors

Flavia Cornacchia, Alessia Fornoni, Anna Rita Plati, Alton Thomas, Yingcai Wang, Luca Inverardi, Liliane J. Striker, Gary E. Striker

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Figure 1

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Genotype of spleen cells and isolated glomeruli. (a) PCR products of +/+...
Genotype of spleen cells and isolated glomeruli. (a) PCR products of +/+ mice migrate as one band (lane 2), whereas those from Os/+ mice migrate as two bands (lane 3) in 2% agarose gels. DNA from the spleens of all +/+ recipients of Os/+ BM was found to contain the Os/+ genotype (representative samples are shown in lanes 4 and 5). Lane 1 contains DNA not exposed to microsatellite primers, and the left lane represents bp size markers. (b) Shown are representative samples of DNA from glomeruli of nine of ten +/+ recipients of Os/+ BM (lanes 4 and 5). Lane 1 contains DNA not exposed to microsatellite primers, and the left lane represents bp size. Lanes 2 and 3 are similar to those in a.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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