4.7 Article

Stem Cell Transplantation Increases Antioxidant Effects in Diabetic Mice

Journal

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
Volume 8, Issue 10, Pages 1335-1344

Publisher

IVYSPRING INT PUBL
DOI: 10.7150/ijbs.4654

Keywords

IBM-BMT plus TT; antioxidant; HO-1; diabetic nephropathy

Funding

  1. Otsuka Pharmaceutical Company, Ltd
  2. NIH [DK068234, HL55601, HL34300]

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Intra bone marrow-bone marrow transplantation (IBM-BMT) + thymus transplantation (TT) has been shown to reduce the incidence of graft versus host disease (GVHD) and restore donor-derived T cell function. In addition, an increase in insulin sensitivity occurred in db/db mice after IBM-BMT + TT treatment. Heme oxygenase (HO)-1 is a stress inducible enzyme which exert antioxidant, antiapoptotic, and immune-modulating properties. We examined whether IBM-BMT + TT could modulate the expression of HO-1 in the kidneys of db/db mice. Six-week-old db/db mice with blood glucose levels higher than 250 mg/dl were treated with IBM-BMT+ TT. Six weeks later, the db/db mice showed decreased body weight, blood glucose levels and insulin, and increased plasma adiponectin levels. The upregulation of HO-1 was associated with significantly (p<0.05) increased levels of peNOS and pAKT, but decreased levels of iNOS in the kidneys of db/db mice. Plasma creatinine levels also decreased (p<0.05), and the expression of type IV collagen was improved. Thus IBM-BMT + TT unregulated the expression of HO-1, peNOS and pAKT, while decreasing iNOS levels in the kidney of db/db mice. This was associated with an improvement in renal function.

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