期刊
DIABETES RESEARCH AND CLINICAL PRACTICE
卷 98, 期 3, 页码 465-473出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.diabres.2012.09.034
关键词
Diabetic nephropathy; Fibrosis; Mesenchymal stem cells; Transforming growth factor-beta 1
资金
- Korea Healthcare Technology R&D Project, Ministry of Health and Welfare [A090289]
- National Research Foundation [2012R1A2A1A03006092]
- Ewha Global Top5 Grant of Ewha Womans University, Republic of Korea
- Korea Health Promotion Institute [A090289] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2012R1A2A1A03006092] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Aims: The present study examined renoprotective effect of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSC) in diabetes. NRK-52E cells were utilized to determine the paracrine effect of hUCB-MSC. Methods: hUCB was harvested with the mother's consent. MSC obtained from the hUCB were injected through the tail vein. Growth arrested and synchronized NRK-52E cells were stimulated with transforming growth factor-beta 1 (TGF-beta 1) in the presence of hUCB-MSC conditioned media. Results: At 4 weeks after the streptozotocin (STZ) injection, diabetic rats showed significantly increased urinary protein excretion, renal and glomerular hypertrophy, fractional mesangial area, renal expression of TGF-beta 1 and alpha-smooth muscle actin, and collagen accumulation but decreased renal E-cadherin and bone morphogenic protein-7 expression, confirming diabetic renal injury. hUCB-MSC effectively prevented diabetic renal injury except renal and glomerular hypertrophy without a significant effect on blood glucose. CM-DiI-labeled hUCB-MSC and immunostaining of PKcs, a human nuclei antigen, confirmed a few engraftment of hUCB-MSC in diabetic kidneys. hUCB-MSC conditioned media inhibited TGF-beta 1-induced extracellular matrix upregulation and epithelial-to-mesenchymal transition in NRK-52E cells in a concentration-dependent manner. Conclusions: These results demonstrate the renoprotective effect of hUCB-MSC in STZ-induced diabetic rats possibly through secretion of humoral factors and suggest hUCB-MSC as a possible treatment modality for diabetic renal injury. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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