Preventive effects of syngeneic bone marrow transplantation on diabetic nephropathy in mice.
Treatment with autologous bone marrow transplantation (ABMT) can change the natural history of diabetes in patients with new-onset Type 1 diabetes (T1D). Effects of syngeneic bone marrow transplantation (syn-BMT) on diabetic nephropathy were studied in streptozotocin-induced diabetic mice. Diabetic mice received sibling's bone marrow on days 3, 10, 20, or 40 after T1D onset, respectively. Renal pathology, levels of oxidative stress, and the expressions of angiotensinogen (AGT), monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor beta 1 (Tgf-beta1) mRNA were investigated. Treatment with syn-BMT when disease was early-onset reduced mesangial area expansion and kidney enlargement; besides, if it is given on day 10, syn-BMT attenuated glomerular hypertrophy. Oxidative stress factors such as catalase (CAT) and superoxide radical anion O(2-) (O(2-)) were markedly maintained by syn-BMT compared to mice without treatment. In diabetic mice without treatment, renal AGT and MCP-1 mRNA were increased, while they were effectively suppressed by syn-BMT. But it showed no changes or even increment in Tgf-beta1 mRNA after syn-BMT. Syn-BMT, if applied when disease was early-onset, ameliorated diabetic renal injury. These preventive effects could be partly via maintaining oxidative stress and expression of AGT and MCP-1 in kidney in streptozotocin-diabetic mice.
Ouyang
Jian
J
Department of Pharmacology, School of Basis Medical Sciences Nanjing Medical University Nanjing, China.
Hu
Gang
G
Wen
Yanting
Y
Zhang
Xin
X
D000808:Angiotensinogen / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D016026:Bone Marrow Transplantation; D002374:Catalase / Q000378:metabolism; D016923:Cell Death; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D003928:Diabetic Nephropathies / Q000517:prevention & control; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000235:genetics
D018932:Chemokine CCL2; D053773:Transforming Growth Factor beta1; D000808:Angiotensinogen; D002374:Catalase