title: Diabetic impairment of C-kit bone marrow stem cells involves the disorders of inflammatory factors, cell adhesion and extracellular matrix molecules.
abstract: Bone marrow stem cells from diabetes mellitus patients exhibit functional impairment, but the relative molecular mechanisms responsible for this impairment are poorly understood. We investigated the mechanisms responsible for diabetes-related functional impairment of bone marrow stem cells by extensively screening the expression levels of inflammatory factors, cell cycle regulating molecules, extracellular matrix molecules and adhesion molecules. Bone marrow cells were collected from type 2 diabetic (db/db) and healthy control (db/m+) mice, and c-kit+ stem cells were purified (purity>85%) for experiments. Compared with the healthy control mice, diabetic mice had significantly fewer c-kit+ stem cells, and these cells had a lower potency of endothelial differentiation; however, the production of the angiogenic growth factor VEGF did not differ between groups. A pathway-focused array showed that the c-kit+ stem cells from diabetic mice had up-regulated expression levels of many inflammatory factors, including Tlr4, Cxcl9, Il9, Tgfb1, Il4, and Tnfsf5, but no obvious change in the expression levels of cell cycle molecules. Interestingly, diabetes-related alterations of the extracellular matrix and adhesion molecules were varied; Pecam, Mmp10, Lamc1, Itgb7, Mmp9, and Timp4 were up-regulated, but Col11a1, Fn1, Admts2, and Itgav were down-regulated. Some of these changes were also confirmed at the protein level by flow cytometry analysis. In conclusion, c-kit+ bone marrow stem cells from diabetic mice exhibited an extensive enhancement of inflammatory factors and disorders of the extracellular matrix and adhesion molecules. Further intervention studies are required to determine the precise role of each molecule in the diabetes-related functional impairment of c-kit+ bone marrow stem cells.
authors: Department of Stem Cell Biology, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan. litaoshe@nagasaki-u.ac.jp
authors: Tao-Sheng
authors: TS
authors: Li
authors: Satoshi
authors: S
authors: Ikeda
authors: Masayuki
authors: M
authors: Kubo
authors: Mako
authors: M
authors: Ohshima
authors: Hiroshi
authors: H
authors: Kurazumi
authors: Yoshihiro
authors: Y
authors: Takemoto
authors: Kazuhiro
authors: K
authors: Ueda
authors: Kimikazu
authors: K
authors: Hamano
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002452:Cell Count; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D003920:Diabetes Mellitus / Q000235:genetics / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006262:Health; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D016326:Extracellular Matrix Proteins; D018836:Inflammation Mediators; D047889:Receptors, Tumor Necrosis Factor, Type II; D051197:Toll-Like Receptor 4; D019009:Proto-Oncogene Proteins c-kit