Angiogenic protein Cyr61 is expressed by podocytes in anti-Thy-1 glomerulonephritis

被引：31

作者：

Sawai, K ^{[1
]}

Mori, K ^{[1
]}

Mukoyama, M ^{[1
]}

Sugawara, A ^{[1
]}

Suganami, T ^{[1
]}

Koshikawa, M ^{[1
]}

Yahata, K ^{[1
]}

Makino, H ^{[1
]}

Nagae, T ^{[1
]}

Fujinaga, Y ^{[1
]}

Yokoi, H ^{[1
]}

Yoshioka, T ^{[1
]}

Yoshimoto, A ^{[1
]}

Tanaka, I ^{[1
]}

Nakao, K ^{[1
]}

机构：

[1] Kyoto Univ, Dept Med & Clin Sci, Grad Sch Med, Sakyo Ku, Kyoto 6068507, Japan

来源：

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2003年 / 14卷 / 05期

关键词：

D O I：

10.1097/01.ASN.0000060576.61218.3D

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Dynamic recovery of glomerular structure occurs after severe glomerular damage in anti-Thy-1 glomerulonephritis (Thy-1 GN), but its mechanism remains to be investigated. To identify candidate genes possibly involved in glomerular reconstruction, screening was performed for genes that are specifically expressed by podocytes and are upregulated in glomeruli of Thy-1 GN. Among them, cysteine-rich protein 61 (Cyr61 or CCN1), a soluble angiogenic protein belonging to the CCN family, was identified. By Northern blot analysis, Cyr61 mRNA was markedly upregulated in glomeruli of Thy-1 GN from day 3 through day 7, when mesangial cell migration was most prominent. By in situ hybridization and immunohistochemistry, Cyr61 mRNA and protein were expressed by proximal straight tubules and afferent and efferent arterioles in normal rat kidneys and were intensely upregulated at podocytes in Thy-1 GN. Platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor-beta1 (TGF-beta1), of which the gene expression in the glomeruli of Thy-1 GN was upregulated in similar time course as Cyr61, induced Cyr61 mRNA expression in cultured podocytes. Furthermore, supernatant of Cyr61-overexpressing cells inhibited PDGF-induced mesangial cell migration. In conclusion, it is shown that Cyr61 is strongly upregulated at podocytes in Thy-1 GN possibly by PDGF and TGF-beta. Cyr61, may be involved in glomerular remodeling as a factor secreted from podocytes to inhibit mesangial cell migration.

引用

页码：1154 / 1163

页数：10

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