Glomerulosclerosis is transmitted by bone marrow-derived mesangial cell progenitors

F. Cornacchia, Alessia Fornoni, A. R. Plati, A. Thomas, Yingcai Wang, Luca A Inverardi, L. J. Striker, G. E. Striker

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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.

Original languageEnglish
Pages (from-to)1649-1656
Number of pages8
JournalJournal of Clinical Investigation
Volume108
Issue number11
DOIs
StatePublished - Dec 29 2001

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Cornacchia, F., Fornoni, A., Plati, A. R., Thomas, A., Wang, Y., Inverardi, L. A., Striker, L. J., & Striker, G. E. (2001). Glomerulosclerosis is transmitted by bone marrow-derived mesangial cell progenitors. Journal of Clinical Investigation, 108(11), 1649-1656. https://doi.org/10.1172/JCI200112916