大鼠增殖性肾小球肾炎中系膜细胞表型的体外特征研究

In vitro characterization of the mesangial phenotype in a proliferative glomerulonephritis of the rat.

作者信息

Harendza S, Behrens U, Zahner G, Schneider A, Stahl R A

机构信息

Department of Medicine, University Hospital Eppendorf, Hamburg, Germany.

出版信息

Nephrol Dial Transplant. 1997 Dec;12(12):2537-41. doi: 10.1093/ndt/12.12.2537.

DOI:10.1093/ndt/12.12.2537

PMID:9430848

Abstract

BACKGROUND

Mesangial cell proliferation is a predominant feature of many glomerular diseases. We have demonstrated in previous studies that an experimental model of mesangial-proliferative glomerulonephritis in the rat could be transferred to in vitro conditions. Using this model we now have been able to study the mesangial phenotype in several subcultures of mesangial cells from nephritic animals regarding proliferation, and the synthesis of prostaglandins and the matrix degrading enzyme MMP-2.

METHODS

Mesangial-proliferative glomerulonephritis was induced in male Sprague-Dawley rats by a single injection of an anti-Thy 1.1 antiserum. Four days after injection of the antiserum glomeruli were isolated and transferred to tissue culture conditions. Immunohistological characterization of cells, cell growth, synthesis of prostaglandins and expression of MMP-2 were studied in the first and second subculture.

RESULTS

Cells from controls and from nephritic animals showed the characteristics of glomerular mesangial cells. Proliferation was decreased in the first and second subculture of cells from nephritic rats compared with controls while there were no immunohistological differences between the cells. Biosynthesis of prostaglandin E2 was significantly increased in subcultures of mesangial cells from nephritic rats. There was also a significant increase in mRNA expression of MMP-2 in the first subculture of mesangial cells from nephritic rats when compared with controls.

CONCLUSIONS

Our data suggest that mesangial cells from nephritic animals show a different phenotype in vitro in several subcultures compared with cells from control animals. This difference can be demonstrated in the patterns of proliferation and biosynthesis of prostaglandins and MMP-2, while immunohistological characteristics of mesangial cells were unchanged between nephritic animals and controls. This experimental in vivo-in vitro approach may serve as a model to study the mesangial phenotype in glomerular diseases.

摘要

背景

系膜细胞增殖是许多肾小球疾病的主要特征。我们在先前的研究中已证明，大鼠系膜增生性肾小球肾炎的实验模型可转移至体外条件下。利用该模型，我们现在能够研究来自肾炎动物的系膜细胞的多个传代培养物中的系膜表型，涉及细胞增殖、前列腺素合成以及基质降解酶MMP-2。

方法

通过单次注射抗Thy 1.1抗血清在雄性Sprague-Dawley大鼠中诱导系膜增生性肾小球肾炎。注射抗血清4天后，分离肾小球并转移至组织培养条件下。在第一代和第二代传代培养物中研究细胞的免疫组织学特征、细胞生长、前列腺素合成以及MMP-2的表达。

结果

来自对照组和肾炎动物的细胞均表现出肾小球系膜细胞的特征。与对照组相比，来自肾炎大鼠的细胞在第一代和第二代传代培养物中的增殖减少，而细胞之间在免疫组织学上无差异。来自肾炎大鼠的系膜细胞传代培养物中前列腺素E2的生物合成显著增加。与对照组相比，来自肾炎大鼠的系膜细胞第一代传代培养物中MMP-2的mRNA表达也显著增加。