CTGF in kidney fibrosis and glomerulonephritis.
CTGF in kidney fibrosis and glomerulonephritis.
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DOI：
10.1186/s41232-018-0070-0
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发表时间：
2018
影响因子：
8.1
通讯作者：
Yokoi H
中科院分区：
文献类型：
--
作者：
Toda N;Mukoyama M;Yanagita M;Yokoi H
肾小球肾炎是导致肾小球炎症的一种常见的终末期肾衰竭原因。严重和长期的炎症可损害肾小球并导致肾纤维化。结缔组织生长因子（CTGF）是CCN基质细胞蛋白家族的成员，由四个结构域组成，其调节其他生长因子的信号传导并促进肾纤维化。CTGF具有4个结构域，可同时与多种因子相互作用。微环境根据细胞和组织的类型以及这些细胞的分化阶段而不同。CTGF对不同类型细胞和组织的不同生物学作用取决于这种微环境的差异。在肾脏中，CTGF在正常条件下以低水平表达，并且其表达被肾纤维化上调。已知CTGF表达在人肾活检样品中肾小球肾炎的毛细血管外和系膜病变中上调。除了参与纤维化之外，CTGF还通过不同的信号传导途径在各种细胞系统中调节炎性介质（包括细胞因子和趋化因子）的表达。在抗肾小球基底膜（GBM）肾小球肾炎中，与对照小鼠相比，系统性CTGF敲除（Rosa-CTGF cKO）小鼠表现出50%的蛋白尿减少和减少的新月体形成和系膜扩张。除了纤维化标志物之外，Ccl 2的肾小球mRNA表达在患有抗GBM肾小球肾炎的对照小鼠中增加，并且这种增加在患有肾炎的Rosa-CTGF cKO小鼠中减少。在Rosa-CTGF cKO小鼠中，肾小球中MAC 2阳性细胞的积累也减少。这些结果表明，CTGF可能需要的CCl 2表达的上调，不仅在抗GBM肾小球肾炎，但也在其他类型的肾小球肾炎，如伊加肾病; CTGF表达和巨噬细胞在系膜区的积累已被记录在这些肾小球疾病。CTGF诱导炎症介质的表达并促进细胞粘附。CTGF通过诱导炎症过程在肾小球肾炎的发展中起重要作用。CTGF是治疗肾小球肾炎的潜在靶点。
Glomerulonephritis, which causes inflammation in glomeruli, is a common cause of end-stage renal failure. Severe and prolonged inflammation can damage glomeruli and lead to kidney fibrosis. Connective tissue growth factor (CTGF) is a member of the CCN matricellular protein family, consisting of four domains, that regulates the signaling of other growth factors and promotes kidney fibrosis. CTGF can simultaneously interact with several factors with its four domains. The microenvironment differs depending on the types of cells and tissues and differentiation stages of these cells. The diverse biological actions of CTGF on various types of cells and tissues depend on this difference in microenvironment. In the kidney, CTGF is expressed at low levels in normal condition and its expression is upregulated by kidney fibrosis. CTGF expression is known to be upregulated in the extra-capillary and mesangial lesions of glomerulonephritis in human kidney biopsy samples. In addition to involvement in fibrosis, CTGF modulates the expression of inflammatory mediators, including cytokines and chemokines, through distinct signaling pathways, in various cell systems. In anti-glomerular basement membrane (GBM) glomerulonephritis, systemic CTGF knockout (Rosa-CTGF cKO) mice exhibit 50% reduction of proteinuria and decreased crescent formation and mesangial expansion compared with control mice. In addition to fibrotic markers, the glomerular mRNA expression of Ccl2 is increased in the control mice with anti-GBM glomerulonephritis, and this increase is reduced in Rosa-CTGF cKO mice with nephritis. Accumulation of MAC2-positive cells in glomeruli is also reduced in Rosa-CTGF cKO mice. These results suggest that CTGF may be required for the upregulation of Ccl2 expression not only in anti-GBM glomerulonephritis but also in other types of glomerulonephritis, such as IgA nephropathy; CTGF expression and accumulation of macrophages in the mesangial area have been documented in these glomerular diseases. CTGF induces the expression of inflammatory mediators and promotes cell adhesion. CTGF plays an important role in the development of glomerulonephritis by inducing the inflammatory process. CTGF is a potentiate target for the treatment of glomerulonephritis.
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影响因子：
19.6
作者：
Kim, JH;Ha, IS;Park, WY
通讯作者：
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