c-Mpl and TPO expression in the human central nervous system neurons inhibits neuronal apoptosis

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.

Injury intensifies T cell mediated graft-versus-host disease in a humanized model of traumatic brain injury

“…Consistent with the protective effects of MSCs on hematopoiesis, exogenous administration of secreted factors including platelet derived growth factor and TPO confer radioprotective effects on the bone marrow via reduction of apoptosis in multipotent hematopoietic stem and progenitor cells as well as mature blood lineages such as megakaryocytes 85 . Perhaps not coincidentally, TPO has also been shown to inhibit neuronal cell death 86 , further supporting existing evidence in the literature that paracrine signaling from MSCs produces positive pleiotropic effects on multiple organ systems.…”

GPIbα is the driving force of hepatic thrombopoietin generation

“…49,50 Both TPO −/− and Mpl −/− mice have decreased numbers of erythroid and myeloid progenitors, 47 and loss of TPO signaling is associated with bone marrow failure and thrombocytopenia, as TPO supports HSC quiescence during adult hematopoiesis. 51,52 TPO can be expressed by multiple cell types such as osteoblasts, megakaryocytes, and stromal cells, and has recently been found in human and rat brain, 53 with an interesting observed protective effect against apoptosis in neural and endothelial cells. 54 However, contributions from hepatocytes above all are specifically critical for HSC maintenance and quiescence.…”

Thrombopoietin Receptor Agonist Eltrombopag Prevents Insulin Resistance and Synaptic Pathology via HIF1α/COX2/Sirt1 Signaling Pathway 

“…These insulin-resistant cells were used for the following experiments. 3 H-2-DG uptake measurement This assay was performed using a modi ed version of a previously described protocol [10]. Brie y, insulin-resistant cells were starved in serum-free, 0.5% (w/v) BSA DMEM for 3 h before treatment.…”

“…TPO reduced brain damage and improved sensorimotor functions. In addition, TPO had a stimulating effect on neural cell proliferation and exerted an antiapoptotic effect [2,3]. TPO improved neurological function and ameliorated brain edema after stroke [4].…”