Diabetic impairment of C-kit + bone marrow stem cells involves the disorders of inflammatory factors, cell adhesion and extracellular matrix molecules

Tao Sheng Li, Satoshi Ikeda, Masayuki Kubo, Mako Ohshima, Hiroshi Kurazumi, Yoshihiro Takemoto, Kazuhiro Ueda, Kimikazu Hamano

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Article numbere25543
JournalPLoS One
Volume6
Issue number10
DOIs
Publication statusPublished - Oct 3 2011
Externally publishedYes

Fingerprint

bone marrow cells
Stem cells
cell adhesion
extracellular matrix
Bone Marrow Cells
Extracellular Matrix
stem cells
Bone
Stem Cells
Molecules
Medical problems
mice
adhesion
diabetes
Adhesion
Cells
cell cycle
Cell Cycle
Flow cytometry
Angiogenesis Inducing Agents

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Diabetic impairment of C-kit + bone marrow stem cells involves the disorders of inflammatory factors, cell adhesion and extracellular matrix molecules. / Li, Tao Sheng; Ikeda, Satoshi; Kubo, Masayuki; Ohshima, Mako; Kurazumi, Hiroshi; Takemoto, Yoshihiro; Ueda, Kazuhiro; Hamano, Kimikazu.

In: PLoS One, Vol. 6, No. 10, e25543, 03.10.2011.

Research output: Contribution to journalArticle

Li, Tao Sheng ; Ikeda, Satoshi ; Kubo, Masayuki ; Ohshima, Mako ; Kurazumi, Hiroshi ; Takemoto, Yoshihiro ; Ueda, Kazuhiro ; Hamano, Kimikazu. / Diabetic impairment of C-kit + bone marrow stem cells involves the disorders of inflammatory factors, cell adhesion and extracellular matrix molecules. In: PLoS One. 2011 ; Vol. 6, No. 10.
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