Abstract

The aim of our study was to investigate the role of bone marrow cells in the phenotypic changes that occur in diabetic nephropathy. Bone marrow cells were obtained from either streptozotocin-induced diabetic or untreated control C3H/He mice and transplanted into control C3H/He mice. Eight weeks after bone marrow cell transplantation, renal morphologic changes and clinical parameters of diabetic nephropathy, including the urine albumin/creatinine ratio and glucose tolerance, were measured in vivo. Expression levels of the genes encoding α1 type IV collagen and transforming growth factor-β1 in the kidney were assayed. Our results demonstrated that glucose tolerance was normal in the recipients of bone marrow transplants from both diabetic and control donors. However, compared with recipients of the control bone marrow transplant, the urinary albumin/creatinine ratio, glomerular size, and the mesangial/glomerular area ratio increased 3.3-fold (p < 0.01), 1.23-fold (p < 0.01), and 2.13-fold (p < 0.001), respectively, in the recipients of the diabetic bone marrow transplant. Expression levels of the genes encoding glomerular α1 type IV collagen and transforming growth factor-β1 were also significantly increased (p < 0.01) in the recipients of the diabetic bone marrow transplant. Our data suggest that bone marrow cells from the STZ-induced diabetic mice can confer a diabetic phenotype to recipient control mice without the presence of hyperglycemia.

Highlights

  • The prevalence of chronic kidney disease in China is 10.8%

  • The results demonstrated that collagen type IV secretion and Col4a1 mRNA expression increased under hyperglycemic conditions in both strains; more dramatic changes were observed in C3H/He mesangial cells

  • After transfer of the bone marrow (BM) cells from the STZ-induced diabetic C3H/He mice to the control C3H/He mice, we observed marked glomerular hypertrophy development in the recipient mice accompanied by normal glucose tolerance and the absence of hyperglycemia

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Summary

Introduction

The prevalence of chronic kidney disease in China is 10.8%. Diabetes is one of the risk factors independently associated with chronic kidney disease [1]. About 25% to 40% of patients with diabetes will develop diabetic nephropathy (DN), characterized by histological changes or a progressive decline in the glomerular filtration rate, within 20 to 25 years of the onset of type 1 or type 2 diabetes mellitus. ECM accumulation and mesangial cell proliferation are pathologic hallmarks or phenotypic changes associated with DN [2]. Hyperglycemia has been implicated in the development of the phenotypic changes associated with DN [3]. Several mechanisms contribute to these phenotypic changes, including high

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