title: Compensatory thrombopoietin production from the liver and bone marrow stimulates thrombopoiesis of living rat megakaryocytes in chronic renal failure.
abstract: OBJECTIVE
  Decreased thrombopoiesis has been ascribed a role in the pathogenesis of uremic bleeding in chronic renal failure (CRF). However, serum thrombopoietin (TPO) levels are usually elevated in CRF patients, suggesting increased thrombopoiesis. The aim of this study was to determine the thrombopoietic activity in CRF.
  
  
  METHODS
  Male Sprague-Dawley rats that underwent 5/6 nephrectomy were used as the model of CRF. Age-matched sham-operated rats were used as controls. Single megakaryocytes were isolated from the rat bone marrow, and their size distribution was examined. Megakaryocyte membrane invaginations were monitored by confocal imaging of di-8-ANEPPS staining, and patch clamp whole-cell recordings of membrane capacitance. TPO gene expression was assessed in various tissues.
  
  
  RESULTS
  Circulating platelet counts and the number of large megakaryocytes were increased in the bone marrow of CRF rats. Massive di-8-ANEPPS staining and increased membrane capacitance in large megakaryocytes demonstrated increased membrane invaginations. Unaffected Kv1.3-channel currents per cell surface area demonstrated unaltered channel densities. TPO transcription was decreased in the renal cortex but increased in the liver and bone marrow of CRF rats.
  
  
  CONCLUSIONS
  Increased thrombopoiesis in CRF was thought to be a reactive mechanism to platelet dysfunction. Increased TPO production from the liver and bone marrow compensated for decreased production from damaged kidneys.
authors.affiliation: Department of Physiology I, Sendai, Japan.
authors.forename: Itsuro
authors.initials: I
authors.lastname: Kazama
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Endo
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Toyama
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Ejima
authors.forename: Shin
authors.initials: S
authors.lastname: Kurosawa
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Murata
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Matsubara
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Maruyama