2014
DOI: 10.1172/jci76838
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Pleiotrophin mediates hematopoietic regeneration via activation of RAS

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Cited by 49 publications
(43 citation statements)
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“…Maintenance of the HSC pool is particularly relevant in the context of hematopoietic injury, such as high dose or repeated rounds of chemotherapy or irradiation, when dormant HSCs transiently proliferate to replenish blood cells and unbalanced HSC proliferation can lead to stem cell exhaustion and long-term myelosuppression 2325 . Consistent with its previously described role in promoting the proliferation of cells, including gonadal and neuronal cells 26,27 , LH significantly enhanced colony formation of LSK cells in cobblestone area-forming cell (CAFC) and colony-forming cell (CFC) assays (Fig.…”
mentioning
confidence: 99%
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“…Maintenance of the HSC pool is particularly relevant in the context of hematopoietic injury, such as high dose or repeated rounds of chemotherapy or irradiation, when dormant HSCs transiently proliferate to replenish blood cells and unbalanced HSC proliferation can lead to stem cell exhaustion and long-term myelosuppression 2325 . Consistent with its previously described role in promoting the proliferation of cells, including gonadal and neuronal cells 26,27 , LH significantly enhanced colony formation of LSK cells in cobblestone area-forming cell (CAFC) and colony-forming cell (CFC) assays (Fig.…”
mentioning
confidence: 99%
“…3d). Although there is a clear need for HSC proliferation to ensure regenerative hematopoiesis 28 , previous reports have also shown that induction of HSC quiescence after high-dose irradiation correlates with increased hematopoietic recovery and enhanced mouse survival 23,25,29,30 . Consistent with this notion, when we analyzed the cell cycle status of HSCs in LHRH-Ant treated mice after L-TBI, we found a significantly higher proportion of Ki-67 − quiescent LT-HSCs (CD150 + CD48 − LSK) in the BM of the LHRH-Ant-treated group as compared to the vehicle group (Fig.…”
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confidence: 99%
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“…Pleiotrophin improves the survival of mice following myeloablative treatment [160]. Pleiotrophin supports the ex vivo expansion of mouse bone marrow HSCs as determined by competitive repopulating assays and supports ex vivo expansion of human cord blood CD34 + CD38  Lin  cells as determined by in a SCID-repopulation assay [75].…”
Section: Pleiotrophinmentioning
confidence: 67%
“…For example, pleiotrophin (PTN) is a neurokine secreted by bone marrow endothelial cells, and studies have suggested that PTN promotes retention and self-renewal of long-term hematopoietic stem cells (LT-HSCs) (80). One CMCR group has recently shown that systemic administration of PTN, even when given at 48 or 96 h postirradiation, not only reduced acute mortality after a lethal dose of total-body irradiation (TBI), but also improved outcome after bone marrow transplant (81). Their investigation has indicated that the underlying mechanism for this efficacy was through the RAS/MEK/ERK pathway, with additional intriguing evidence suggesting an alternative mechanism related to PTN’s role in promoting retention of LT-HSCs in a quiescent phase, i.e., allowing more time for DNA repair.…”
Section: Countermeasure Efforts: Targets/approaches/alternativesmentioning
confidence: 99%