Localization and Regulation of Thrombopoietin mRNA Expression in Human Kidney, Liver, Bone Marrow, and Spleen Using In Situ Hybridization

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Abstract
Thrombopoietin (TPO) is the primary hematopoietic growth factor involved in the regulation of platelet production. Although the kidney, liver, bone marrow (BM), and spleen have been identified as the major sources of TPO production, the precise cellular location of TPO mRNA expression in these tissues remains unknown. We have identified the cells expressing TPO mRNA in the human kidney, liver, and BM using an in situ hybridization assay. In the BM of individuals with normal platelet counts, the hybridization signal was too weak to allow identification of the TPO mRNA expressing cells. However, in thrombocytopenic subjects with aplastic anemia, postchemotherapy marrow aplasia, and immune thrombocytopenia, the stromal cells showed strong TPO mRNA expression. In the human subjects with normal platelet counts, the cells of the proximal convoluted tubules of the kidney showed consistent positive staining whereas the signal in the cells of the distal convoluted tubules was less consistent. Strong hybridization signal was also evident in the hepatocytes. The hybridization signal in the spleen, even in thrombocytopenic subjects, was too weak to allow confident identification of the cells expressing TPO mRNA. In all subjects, the interstitial cells and endothelial cells of the liver and spleen, the renal peritubular cells, and the hematopoietic precursor cells of the BM showed no TPO mRNA expression. Our data suggest that TPO mRNA expression in the human BM may be modulated by platelet mass.