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Isogenic mesenchymal stem cells transplantation improves a rat model of chronic aristolochic acid nephropathy via upregulation of hepatic growth factor and downregulation of transforming growth factor β1

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Abstract

Chronic aristolochic acid (AA) nephropathy (CAAN) caused by intake of AA-containing herbs is difficult to treat. We evaluated the therapeutic effect of bone marrow (BM) mesenchymal stem cells (MSCs) on a rat model of CAAN. Female Wistar rats were fed with decoction of Caulis Aristolochia manshuriensis by intragastric administration. MSCs were prepared from BM of male Wistar rats and injected into female CAAN rats through tail vein. Body weight, renal function, and urinary excretion of these CAAN rats were monitored before killing at the end of the 20th week. Blood, urine, and tissue samples were collected from experimental (MSC and non-MSC) and normal control groups. All animals developed renal fibrosis after 12 weeks of intake of AA-containing decoction. Fibrosis in the MSC groups was significantly reduced as examined with light and electron microscopy. Blood urea nitrogen, serum creatinine, and urine protein levels were significantly reduced and hemoglobin levels were improved in the MSC group as compared with the non-MSC group (p < 0.01). The expression of TGF-β1 mRNA and protein was reduced but hepatic growth factor (HGF) was increased in the MSC group compared with the non-MSC group, but still higher than the normal control level as measured by immunochemical, RT-PCR, and western blotting assays (p < 0.01). The renal fibrosis of CAAN could be protected by isogenic MSC transplantation, probably via upregulation of HGF and downregulation of TGF-β1.

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Abbreviations

CAAN:

Chronic aristolochic acid nephropathy

AA:

Aristolochic acid

MSCs:

Mesenchymal stem cells

TGF-β1:

Transforming growth factor

HGF:

Hepatocyte growth factor

RP-HPLC:

Reversed-phase high-performance liquid chromatography

IOD:

Integrated optical density

TIMP-1:

Metalloproteinase-1

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Acknowledgments

This work was supported by Liaoning Province Department of education scientific research project (No: L2010568).

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None declared.

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Authors and Affiliations

  1. Departments of Pediatrics, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning, China

    Wei Li & Hong Jiang

  2. Departments of Nephrology, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning, China

    Jiang-Min Feng

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  1. Wei Li
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  2. Hong Jiang
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  3. Jiang-Min Feng
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Correspondence to Jiang-Min Feng.

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Li, W., Jiang, H. & Feng, JM. Isogenic mesenchymal stem cells transplantation improves a rat model of chronic aristolochic acid nephropathy via upregulation of hepatic growth factor and downregulation of transforming growth factor β1. Mol Cell Biochem 368, 137–145 (2012). https://doi.org/10.1007/s11010-012-1352-5

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  • DOI: https://doi.org/10.1007/s11010-012-1352-5

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