肾移植纤维化与金属蛋白酶组织抑制剂信使核糖核酸的移植内表达相关。

Renal transplant fibrosis correlates with intragraft expression of tissue inhibitor of metalloproteinase messenger RNA.

作者信息

Nicholson M L, Waller J R, Bicknell G R

机构信息

University Department of Surgery, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK.

出版信息

Br J Surg. 2002 Jul;89(7):933-7. doi: 10.1046/j.1365-2168.2002.02118.x.

DOI:10.1046/j.1365-2168.2002.02118.x

PMID:12081746

Abstract

BACKGROUND

Chronic renal allograft nephropathy is characterized by an abnormal accumulation of extracellular matrix proteins in the glomeruli and tubulo-interstitium. The aim of this study was to determine the relationship between intragraft expression of the genes controlling the accumulation of extracellular matrix and the development of chronic renal allograft nephropathy in human renal transplants.

METHODS

Forty renal allografts with stable renal function were biopsied 6 months after transplantation. Single glomeruli were plucked from the surface of these protocol biopsies and total messenger RNA (mRNA) was extracted. Reverse transcriptase-polymerase chain reaction was used to study the intragraft expression of several fibrosis-associated genes (collagen III, collagen IValpha2, matrix metalloproteinase (MMP) 2, tissue inhibitors of metalloproteinases (TIMPs) 1 and 2, tenascin and transforming growth factor (TGF) beta1). The level of tubulo-interstitial fibrosis was measured by quantitative immunostaining of collagen III.

RESULTS

There were positive correlations between the level of tubulo-interstitial collagen III immunostaining and intragraft expression of the genes for TIMP-1 (rs= 0.70, P < 0.02) and TIMP-2 (rs = 0.59, P < 0.02). Interstitial fibrosis was also strongly correlated with the levels of TGF-beta mRNA (rs = 0.67, P < 0.002). Finally, TIMP-1 expression increased with TGF-beta expression (rs = 0.77, P < 0.002).

CONCLUSION

Failure of extracellular matrix degradation may be an important molecular mechanism in the pathogenesis of chronic renal allograft damage.

摘要

背景

慢性肾移植肾病的特征是细胞外基质蛋白在肾小球和肾小管间质中异常积聚。本研究的目的是确定控制细胞外基质积聚的基因在移植肾内的表达与人类肾移植中慢性肾移植肾病发生发展之间的关系。

方法

40例肾功能稳定的肾移植受者在移植后6个月接受活检。从这些方案活检标本的表面摘取单个肾小球，提取总信使核糖核酸（mRNA）。采用逆转录-聚合酶链反应研究几种纤维化相关基因（Ⅲ型胶原、Ⅳ型胶原α2链、基质金属蛋白酶（MMP）2、金属蛋白酶组织抑制剂（TIMP）1和2、腱糖蛋白和转化生长因子（TGF）β1）在移植肾内的表达。通过Ⅲ型胶原的定量免疫染色测量肾小管间质纤维化程度。

结果

肾小管间质Ⅲ型胶原免疫染色水平与移植肾内TIMP-1基因表达（rs = 0.70，P < 0.02）和TIMP-2基因表达（rs = 0.59，P < 0.02）呈正相关。间质纤维化也与TGF-β mRNA水平密切相关（rs = 0.67，P < 0.002）。最后，TIMP-1表达随TGF-β表达增加（rs = 0.77，P < 0.002）。