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, expansion of the mesangial matrix in the glomerulus, and atrophy of the renal tubuli. Plasma transforming growth factor (TGF)-beta1 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.