Renal and Hematological Effects of CLCF-1, a B-Cell-Stimulating Cytokine of the IL-6 Family.
Renal and Hematological Effects of CLCF-1, a B-Cell-Stimulating Cytokine of the IL-6 Family.
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DOI：
10.1155/2015/714964
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发表时间：
2015
影响因子：
4.1
通讯作者：
Gauchat JF
中科院分区：
文献类型：
--
作者：
Savin VJ;Sharma M;Zhou J;Gennochi D;Fields T;Sharma R;McCarthy ET;Srivastava T;Domen J;Tormo A;Gauchat JF
CLCF-1是已知用于B细胞刺激和神经营养特性的细胞因子。我们已经确定CLCF-1作为一个潜在的有害因素，在人类肾脏疾病局灶节段性肾小球硬化症（FSGS）。我们在体外和体内研究中研究了其对肾细胞和肾功能的影响。方法包括测量CLCF-1对JAK/STAT途径的靶分子的磷酸化、对培养的足细胞中的细胞骨架和细胞形态、对分离的大鼠肾小球的白蛋白渗透性以及对急性或慢性CLCF-1注射后的组织磷酸化和尿白蛋白的影响。此外，进行细胞分选以确定正常小鼠的脾和骨髓中表达CLCF-1的细胞的存在以及CLCF-1输注对脾B细胞群的影响。CLCF-1增加多种细胞类型中STAT 3的磷酸化，活化足细胞导致板状伪足的形成和基底应力纤维的减少，增加肾小球白蛋白渗透性，以及增加外周血细胞和肾皮质的STAT 3磷酸化。CLCF-1增加小鼠的尿白蛋白/肌酐比，并增加小鼠脾脏中IgG的B细胞表达。我们得出结论，CLCF-1具有潜在的重要的全身效应，改变足细胞功能，并可能导致肾功能不全和蛋白尿。
CLCF-1 is a cytokine known for B-cell stimulation and for neurotrophic properties. We have identified CLCF-1 as a potential injurious factor in the human renal disease focal segmental glomerulosclerosis (FSGS). We investigated its effects on renal cells and renal function in in vitro and in vivo studies. Methods include measurement of the effect of CLCF-1 on phosphorylation of target molecules of the JAK/STAT pathway, on cytoskeleton and cell morphology in cultured podocytes, on albumin permeability of isolated rat glomeruli, and on tissue phosphorylation and urine albumin after acute or chronic CLCF-1 injection. In addition, cell sorting was performed to determine the presence of cells expressing CLCF-1 in spleen and bone marrow of normal mice and the effect of CLCF-1 infusion on splenic B-cell populations. CLCF-1 increased phosphorylation of STAT3 in multiple cell types, activated podocytes leading to formation of lamellipodia and decrease in basal stress fibers, increased glomerular albumin permeability, and increased STAT3 phosphorylation of peripheral blood cells and renal cortex. CLCF-1 increased urine albumin/creatinine ratio in mice and increased B-cell expression of IgG in mouse spleen. We conclude that CLCF-1 has potentially important systemic effects, alters podocyte function, and may contribute to renal dysfunction and albuminuria.
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影响因子：
13.2
作者：
Hariharan, S;Peddi, VR;Adams, MB
通讯作者：
Adams, MB
影响因子：
13.6
作者：
Boyer, Olivia;Benoit, Genevieve;Antignac, Corinne
通讯作者：
Antignac, Corinne
影响因子：
4.8
作者：
Auernhammer, CJ;Isele, NB;Engelhardt, D
通讯作者：
Engelhardt, D
影响因子：
13.6
作者：
Coward, RJM;Foster, RR;Saleem, MA
通讯作者：
Saleem, MA
影响因子：
56.9
作者：
Darnell, JE
通讯作者：
Darnell, JE