Abstract
Thrombopoietin (TPO) is a growth factor for the megakaryocytic/platelet lineage. In this study, we investigated the expression of TPO and its receptor, c-Mpl, in the human central nervous system (CNS) and their roles after a neural insult. Our results demonstrate that both TPO and c-Mpl are expressed in the neurons of the human CNS. TPO was also detected in human cerebrospinal fluid. TPO was found to be neuroprotective in hypoxic-ischemic neonatal rat brain models. In these rat models, treatment with TPO reduced brain damage and improved sensorimotor functions. In addition, TPO promoted C17.2 cell proliferation through activation of the PI3K/Akt signaling pathway. Via the Bcl-2/BAX signaling pathway, TPO exerted an antiapoptotic effect by suppressing mitochondrial membrane potentials. Taken together, our results indicate that TPO is neuroprotective in the CNS.
Highlights
Thrombopoietin (TPO) is a primary regulator of megakaryopoiesis and thrombopoiesis and is a ligand for the receptor c-Mpl [1, 2]
TPO protein was detected in human cerebrospinal fluid (CSF) (n = 10) and blood plasma (n = 10) (Table 1)
We have found that plasma TPO levels in patients with acute cerebral infarction are significantly increased, indicating that TPO may play an important role in central nervous system (CNS) injury
Summary
Thrombopoietin (TPO) is a primary regulator of megakaryopoiesis and thrombopoiesis and is a ligand for the receptor c-Mpl [1, 2]. TPO was first purified in 1994, and since much has been learned about its structure, functions, and clinical uses [3, 4]. TPO promotes megakaryocyte lineage differentiation [5] and platelet production [6, 7]. TPO is essential for bone marrow hematopoietic stem cell (HSC) maintenance. When TPO was deleted from hepatocytes in TPODsRedCreER knock-in mice, bone marrow HSCs were depleted [8]. TPO protects endothelial cells from apoptosis [9, 10]. We have reported that TPO has an antiapoptotic effect in cardiomyocytes [11]
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