Existence of a regulatory loop between MCP-1 and TGF-beta in glomerular immune injury.
Existence of a regulatory loop between MCP-1 and TGF-beta in glomerular immune injury.
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MCP-1 和 TGF-β 在肾小球免疫损伤中存在调节环路。
DOI：
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
R. Stahl
中科院分区：
文献类型：
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作者：
G. Wolf;T. Jocks;G. Zahner;U. Panzer;R. Stahl
肾小球单核细胞趋化蛋白-1（MCP-1）上调，随后单核细胞流入，最终导致细胞外基质沉积，是许多类型肾小球肾炎的常见后遗症。然而，目前还不完全清楚MCP-1的早期表达如何与肾小球硬化的后期发展相关联。由于转化生长因子-β（TGF-β）是细胞外基质蛋白的关键调节因子，我们假设在早期肾小球MCP-1诱导和随后的TGF-β表达之间可能存在调节环。为了避免干扰其他细胞因子，可能会释放浸润单核细胞，离体大鼠肾脏灌注与多克隆抗胸腺细胞-1抗血清（ATS）和大鼠血清（RS）作为补体来源，以诱导肾小球损伤。ATS-RS灌流后，肾TGF-β蛋白和mRNA表达强烈刺激。这种效果减弱与中和抗MCP-1的共灌注，但与重组MCP-1蛋白灌注部分模仿。另一方面，肾MCP-1的表达和生产刺激ATS-RS的管理。另外灌注抗TGF-β抗体进一步加剧了这种增加，而应用重组TGF-β蛋白减少MCP-1的形成。我们的数据显示了一个内在的调节环，其中增加的MCP-1水平刺激TGF-β形成在驻地肾小球细胞浸润的免疫活性细胞的情况下。
Glomerular upregulation of monocyte chemotactic protein-1 (MCP-1), followed by an influx of monocytes resulting eventually in extracellular matrix deposition is a common sequel of many types of glomerulonephritis. However, it is not entirely clear how early expression of MCP-1 is linked to the later development of glomerulosclerosis. Because transforming growth factor-beta (TGF-beta) is a key regulator of extracellular matrix proteins, we hypothesized that there might be a regulatory loop between early glomerular MCP-1 induction and subsequent TGF-beta expression. To avoid interference with other cytokines that may be released from infiltrating monocytes, isolated rat kidneys were perfused with a polyclonal anti-thymocyte-1 antiserum (ATS) and rat serum (RS) as a complement source to induce glomerular injury. Renal TGF-beta protein and mRNA expressions were strongly stimulated after perfusion with ATS-RS. This effect was attenuated by coperfusion with a neutralizing anti-MCP-1 but was partly mimicked by perfusion with recombinant MCP-1 protein. On the other hand, renal MCP-1 expression and production were stimulated by administration of ATS-RS. Additional perfusion with an anti-TGF-beta antibody further aggravated this increase, whereas application of recombinant TGF-beta protein reduced MCP-1 formation. Our data demonstrate an intrinsic regulatory loop in which increased MCP-1 levels stimulate TGF-beta formation in resident glomerular cells in the absence of infiltrating immune competent cells.
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影响因子：
15.9
作者：
Zisman, DA;Kunkel, SL;Standiford, TJ
通讯作者：
Standiford, TJ
影响因子：
15.9
作者：
OKUDA, S;LANGUINO, LR;BORDER, WA
通讯作者：
BORDER, WA
趋化因子阻断作为肾脏疾病的治疗方法。
影响因子：
3.2
作者：
Rovin,BH
通讯作者：
Rovin,BH
DOI：
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发表时间：
--
期刊：
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影响因子：
--
作者：
通讯作者：
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DOI：
10.1097/01.asn.0000108520.63445.e0
发表时间：
2004-02-01
影响因子：
13.6
作者：
Stambe, C;Nikolic-Paterson, DJ;Atkins, RC
通讯作者：
Atkins, RC