Chronic thrombopoietin overexpression induces mesangioproliferative glomerulopathy in mice

We previously reported that mice transgenic (Tg) for thrombopoietin (TPO) developed progressive fibrosis and osteosclerosis of the bone marrow. Here, we show that TPO‐overexpressing mice also exhibited notable histological changes in the kidneys, including an increased number of mesangial cells, exp...

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Bibliographic Details
Published in:American journal of hematology 2007-09, Vol.82 (9), p.802-806
Main Authors: Shimoda, Haruko K., Yamamoto, Masahiro, Shide, Kotaro, Kamezaki, Kenjirou, Matsuda, Tadashi, Ogawa, Katsuhiro, Harada, Mine, Shimoda, Kazuya
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Glomerular Mesangium - metabolism
Glomerular Mesangium - pathology
Glomerulonephritis, Membranoproliferative - etiology
Glomerulonephritis, Membranoproliferative - metabolism
Glomerulonephritis, Membranoproliferative - pathology
Hematologic and hematopoietic diseases
Histocytochemistry
Medical sciences
Mice
Mice, Transgenic
Organ Size
Platelet-Derived Growth Factor - analysis
Proto-Oncogene Proteins c-sis
Thrombopoietin - genetics
Thrombopoietin - metabolism
Transforming Growth Factor beta1 - blood
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Summary:We previously reported that mice transgenic (Tg) for thrombopoietin (TPO) developed progressive fibrosis and osteosclerosis of the bone marrow. Here, we show that TPO‐overexpressing mice also exhibited notable histological changes in the kidneys, including an increased number of mesangial cells, expansion of the mesangial matrix in the glomerulus, and atrophy of the renal tubuli. Plasma transforming growth factor (TGF)‐β1 and platelet‐derived growth factor (PDGF)‐BB, which could induce mesangioproliferative responses in glomeruli, were both elevated in TPO Tg mice, even though TPO itself has no effect on mesangial cells due to their lack of c‐Mpl. The mesangial proliferative change in TPO Tg mice was thought to be induced by the elevation of these cytokines. In conclusion, our finding that TPO‐overexpressing mice developed mesangioproliferative glomerulopathy might represent an undesirable effect of chronically elevated TPO in vivo, which should be taken into consideration before new TPO‐like growth factors become available in clinical practice. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.
ISSN:0361-8609
1096-8652
DOI:10.1002/ajh.20970