Hematopoietic recovery following chemotherapy is improved by BADGE-induced inhibition of adipogenesis
| Autor: | Meng-Qing Wu, Zi-Jian Li, Rong-Jia Zhu, Kai-Yan Liu, Yao Zhang |
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| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Stromal cell Gene Expression Antineoplastic Agents Biology chemistry.chemical_compound Leukocyte Count Mice In vivo Bone Marrow Internal medicine Adipocyte medicine Adipocytes Animals Benzhydryl Compounds Cell Proliferation Colony-forming unit Adipogenesis Hyperplasia Cytarabine Cell Differentiation Hematology Hematopoietic Stem Cells Hypoxia-Inducible Factor 1 alpha Subunit Hematopoiesis PPAR gamma Haematopoiesis medicine.anatomical_structure Endocrinology chemistry Epoxy Compounds Female Bone marrow Stem cell |
| Zdroj: | International journal of hematology. 97(1) |
| ISSN: | 1865-3774 |
| Popis: | This study was designed to investigate the role of increased adipocytes in the bone marrow (BM) niche induced by high-dose chemotherapy in hematopoietic recovery. Arabinosylcytosine (Ara-C) was administered to adult C57BL/6J mice to induce adipogenesis in the BM. We investigated the effects of adipogenesis on hematopoietic recovery following chemotherapy, using the peroxisome proliferator-activated receptor gamma inhibitor, bisphenol A diglycidyl ether (BADGE). Adipocyte hyperplasia could be induced by Ara-C treatment in BM and inhibited by BADGE. The accelerated recovery of leukocyte counts, increased colony forming units, and a higher proportion of Ki67(+)CD45(+) BM cells and Ki67(+)Lin(-)Sca1(+)c-kit(+) hematopoietic stem cells were observed in the long bone marrow of adipocyte-inhibited mice, as well as an increase in the number of CD45(+) BM cells in the tail fatty marrow compared to controls. Adipocytes participated in creating a distinctive niche for hematopoietic cells. In addition, lower expression of stromal cell-derived factor-1α and hypoxia-inducible factor-1 alpha were detected in the BADGE-treated group. These results indicate that hematopoietic recovery is improved following chemotherapy in adipogenesis-inhibited mice. In addition, adipocytes may create an individual niche that affects the proliferation and migration of hematopoietic cells in vitro and in vivo. |
| Databáze: | OpenAIRE |
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