title: H2S protects against fatal myelosuppression by promoting the generation of megakaryocytes/platelets.
abstract: BACKGROUND
  Our previous pilot studies aimed to examine the role of hydrogen sulfide (H2S) in the generation of endothelial progenitor cells led to an unexpected result, i.e., H2S promoted the differentiation of certain hematopoietic stem/progenitor cells in the bone marrow. This gave rise to an idea that H2S might promote hematopoiesis.
  
  
  METHODS
  To test this idea, a mice model of myelosuppression and cultured fetal liver cells were used to examine the role of H2S in hematopoiesis.
  
  
  RESULTS
  H2S promoted the generation of megakaryocytes, increased platelet levels, ameliorate entorrhagia, and improved survival. These H2S effects were blocked in both in vivo and in vitro models with thrombopoietin (TPO) receptor knockout mice (c-mpl(-/-) mice). In contrast, H2S promoted megakaryocytes/platelets generation in both in vivo and in vitro models with TPO knockout mice (TPO(-/-) mice).
  
  
  CONCLUSIONS
  H2S is a novel promoter for megakaryopoiesis by acting on the TPO receptors but not TPO to generate megakaryocytes/platelets.
authors.affiliation: Shanghai Key Laboratory of Bioactive Small Molecules and Research Center on Aging and Medicine, Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, 138 Yi Xue Yuan Road, Shanghai, 200032, China.|Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine in Henan Province, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China.
authors.forename: Huan-Di
authors.initials: HD
authors.lastname: Liu
authors.affiliation: Shanghai Key Laboratory of Bioactive Small Molecules and Research Center on Aging and Medicine, Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, 138 Yi Xue Yuan Road, Shanghai, 200032, China.
authors.forename: Ai-Jie
authors.initials: AJ
authors.lastname: Zhang
authors.affiliation: Shanghai Key Laboratory of Bioactive Small Molecules and Research Center on Aging and Medicine, Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, 138 Yi Xue Yuan Road, Shanghai, 200032, China.|Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Xu
authors.affiliation: Shanghai Key Laboratory of Bioactive Small Molecules and Research Center on Aging and Medicine, Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, 138 Yi Xue Yuan Road, Shanghai, 200032, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Shanghai Key Laboratory of Bioactive Small Molecules and Research Center on Aging and Medicine, Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, 138 Yi Xue Yuan Road, Shanghai, 200032, China. yczhu@shmu.edu.cn.
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005333:Fetus / Q000166:cytology; D006410:Hematopoiesis / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008533:Megakaryocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D053628:Receptors, Thrombopoietin / Q000235:genetics / Q000378:metabolism; D013440:Sulfides / Q000494:pharmacology; D016019:Survival Analysis; D013926:Thrombopoietin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
chemical_list: D053628:Receptors, Thrombopoietin; D013440:Sulfides; D013926:Thrombopoietin; C025451:sodium bisulfide; D006862:Hydrogen Sulfide