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  • Title: [The role of Cubilin in albumin-induced MCP-1, RANTES expression by renal tubular epithelial cells].
    Author: He YN, Yang JR, Jiang JX, Zhou P, Liu DW, Shen HY, Chen J.
    Journal: Zhonghua Yi Xue Za Zhi; 2004 Nov 02; 84(21):1804-9. PubMed ID: 15631778.
    Abstract:
    OBJECTIVE: To study the molecular mechanism of albumin-induced MCP-1 and RANTES expression by renal tubular epithelial cells (RTECs). METHODS: Ten nephrotic syndrome patients and eight hematuric patients were collected into this study. In vivo, albumin deposition, MCP-1 and RANTES expression in kidney tissues from these patients were examined by immunochemistry. In vitro, expression vector harboring sense or antisense cubilin gene fragment was transfected into HK2 cells with lipofectin DOTAP. Endocytosis of FITC labeled human serum albumin (FITC-HSA) by RTECs was detected by fluorescent microscope. MCP-1 and RANTES expression were determined by Western blot analysis. RESULTS: Under the light microscope, normal histological configuration was observed in the hematuric patients; obvious tubulointerstitial lesions such as inflammatory cell infiltration, tubular cell atrophy and tubulointerstitial fibrosis were shown in the nephrotic syndrome patients. By immunohistochemistry study, only a small quantity of albumin were found within the RTECs in the hematuric patients; but a large amount of albumin were seen within the RTECs and interstitium in the nephrotic syndrome patients. MCP-1 and RANTES were weakly expressed in the hematuric patients; but very strongly expressed in the nephrotic syndrome patients. In vitro, cubilin expression by HK2 cells was obviously inhibited by antisense cubilin (pCDNA-ACUB). HSA-FITC uptake was lower in HK2 cells transfected with pCDNA-ACUB than in the cells harboring sense cubilin (pCDNA-CUB) or Vector (pCDNA3.1(+)). Both MCP-1 and RANTES expression were significantly suppressed in HK2 cells transtected with pCDNA-ACUB when compared with the cells harboring pCDNA-CUB or pCDNA3.1(+), respectively. CONCLUSION: Excessive albumin reabsorption may have close relationship with over-expression of MCP-1 and RANTES by RTECs, which might be responsible for the tubulointersitial injury associated with proteinuria. Cubilin may play a key role in regulation of this process.
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