Induction of monocyte chemoattractant protein-1 in proximal tubule cells by urinary protein.

Induction of monocyte chemoattractant protein-1 in proximal tubule cells by urinary protein.
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尿蛋白诱导近曲小管细胞中的单核细胞趋化蛋白-1。

DOI:
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发表时间:
1997
影响因子:
13.6
通讯作者:
D. Harris
D. Harris
中科院分区:
医学1区
文献类型:
--
作者:
Y. Wang;J. Chen;L. Chen;Y. Tay;G. Rangan;D. Harris

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细胞因子在慢性肾功能衰竭(CRF)细胞外基质的合成和沉积中起关键作用。单核细胞趋化蛋白(MCP)-1的促炎特性使其成为CRF间质炎症产生的理想候选细胞因子。为了研究蛋白尿在诱导近端肾小管(PT)MCP-1中的可能作用,在含有多种蛋白的培养基中的原代培养的PT细胞的汇合单层中,通过北方印迹和逆转录PCR测量MCP-1 mRNA水平。PT细胞响应牛血清白蛋白(BSA)、脱脂BSA(dBSA; 0.5至30 mg/ml)、全转铁蛋白和脱铁转铁蛋白(1至8 mg/ml)产生MCP-1 mRNA。未刺激的PT细胞表达极低水平的MCP-1 mRNA,可通过逆转录PCR检测到,但不能通过北方印迹检测到。MCP-1 mRNA的表达在dBSA暴露后4 h内达到峰值(比对照组高6倍),并持续暴露至少24 h。从培养基中去除dBSA导致MCP-1 mRNA表达迅速下降。dBSA诱导的MCP-1表达被赖氨酸抑制,赖氨酸是一种蛋白质摄取的抑制剂,并通过凝胶和尺寸选择性过滤纯化的dBSA再现。dBSA影响MCP-1的表达在转录水平和可能的翻译,证明废除MCP-1的放线菌素D和超诱导蛋白质合成抑制剂放线菌酮。MCP-1蛋白的浓度响应dBSA添加到PT细胞的顶面是2.4倍以上,在基底侧比在顶媒体,表明MCP-1蛋白的基底侧分泌。总之,PT细胞MCP-1 mRNA和蛋白表达上调白蛋白和转铁蛋白,在类似的蛋白尿的浓度。这种效应可以解释CRF中蛋白尿和间质炎症之间的联系。
Cytokines play a pivotal role in synthesis and deposition of extracellular matrix in chronic renal failure (CRF). The proinflammatory properties of monocyte chemoattractant protein (MCP)-1 make it an ideal candidate cytokine for the production of interstitial inflammation in CRF. To investigate the possible role of proteinuria in inducing proximal tubular (PT) MCP-1, MCP-1 mRNA levels were measured by Northern blot and reverse transcription PCR in confluent monolayers of PT cells in primary culture in media containing a variety of proteins. PT cells produced MCP-1 mRNA in response to bovine serum albumin (BSA), delipidated BSA (dBSA; 0.5 to 30 mg/ml), holotransferrin, and apotransferrin (1 to 8 mg/ml). Unstimulated PT cells expressed very low levels of MCP-1 mRNA, detectable by reverse transcription PCR but not by Northern blot. The expression of MCP-1 mRNA reached a peak (sixfold greater than control) within 4 h of exposure to dBSA and was maintained for at least 24 h with continued exposure. Removal of dBSA from the media led to a rapid decline in MCP-1 mRNA expression. dBSA-induced MCP-1 expression was inhibited by lysine, an inhibitor of protein uptake, and reproduced by dBSA purified by gel and size-selective filtration. dBSA influenced MCP-1 expression at the level of transcription and probably translation, as evidenced by abrogation of MCP-1 by actinomycin D and superinduction with the protein synthesis inhibitor cycloheximide. The concentration of MCP-1 protein in response to dBSA added to the apical surface of PT cells was 2.4-fold greater in basolateral than in apical media, indicating basolateral secretion of MCP-1 protein. In summary, PT cell MCP-1 mRNA and protein expression are upregulated by albumin and transferrin, in concentrations similar to those of proteinuric urine. This effect could explain the link between proteinuria and interstitial inflammation in CRF.
前蛋白尿和蛋白尿糖尿病大鼠的肾小球滤过和肾小管白蛋白重吸收。
DOI: 10.1172/jci116638
发表时间: 1993
期刊: The Journal of clinical investigation
影响因子: --
作者:
Tucker,BJ;Rasch,R;Blantz,RC
通讯作者: Blantz,RC
DOI: 10.1016/s0272-6386(96)90097-9
发表时间: 1996-05-01
影响因子: 13.2
作者:
Rovin, BH;Doe, N;Tan, LC
通讯作者: Tan, LC
干扰素-γ对人肾皮质上皮细胞来源的单核细胞趋化肽-1的调节。
DOI: 10.1038/ki.1993.211
发表时间: 1993
影响因子: 19.6
作者:
Schmouder,RL;Strieter,RM;Kunkel,SL
通讯作者: Kunkel,SL
DOI: 10.1038/ki.1994.222
发表时间: 1994-06-01
影响因子: 19.6
作者:
KEESFOLTS, D;SADOW, JL;SCHREINER, GF
通讯作者: SCHREINER, GF
DOI: 10.1152/ajprenal.1990.258.5.f1354
发表时间: 1990-05-01
影响因子: --
作者:
NATH, KA;CROATT, AJ;HOSTETTER, TH
通讯作者: HOSTETTER, TH