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Journal of Immunology Research
Volume 2015, Article ID 714964, 11 pages
Research Article

Renal and Hematological Effects of CLCF-1, a B-Cell-Stimulating Cytokine of the IL-6 Family

1Renal Research Laboratory, Research and Development, MBRF and Kansas City VA Medical Center, Kansas City, MO 64128, USA
2Kidney Institute, University of Kansas Medical Center, Kansas City, KS 66160, USA
3Section of Nephrology, Children’s Mercy Hospital and University of Missouri at Kansas City, Kansas City, MO 64108, USA
4Section of Cardiac Surgery, Children’s Mercy Hospital and University of Missouri at Kansas City, Kansas City, MO 64108, USA
5Department of Pharmacology, University of Montreal, Montreal, QC, Canada H3T 1J4

Received 1 March 2015; Accepted 13 May 2015

Academic Editor: Clelia M. Riera

Copyright © 2015 Virginia J. Savin et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.