title: Renal and Hematological Effects of CLCF-1, a B-Cell-Stimulating Cytokine of the IL-6 Family.
abstract: 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.
authors.affiliation: Renal Research Laboratory, Research and Development, MBRF and Kansas City VA Medical Center, Kansas City, MO 64128, USA ; Kidney Institute, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Virginia J
authors.initials: VJ
authors.lastname: Savin
authors.affiliation: Renal Research Laboratory, Research and Development, MBRF and Kansas City VA Medical Center, Kansas City, MO 64128, USA ; Kidney Institute, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Mukut
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Renal Research Laboratory, Research and Development, MBRF and Kansas City VA Medical Center, Kansas City, MO 64128, USA.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Renal Research Laboratory, Research and Development, MBRF and Kansas City VA Medical Center, Kansas City, MO 64128, USA.
authors.forename: David
authors.initials: D
authors.lastname: Gennochi
authors.affiliation: Kidney Institute, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Fields
authors.affiliation: Renal Research Laboratory, Research and Development, MBRF and Kansas City VA Medical Center, Kansas City, MO 64128, USA.
authors.forename: Ram
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Kidney Institute, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Ellen T
authors.initials: ET
authors.lastname: McCarthy
authors.affiliation: Renal Research Laboratory, Research and Development, MBRF and Kansas City VA Medical Center, Kansas City, MO 64128, USA ; Section of Nephrology, Children's Mercy Hospital and University of Missouri at Kansas City, Kansas City, MO 64108, USA.
authors.forename: Tarak
authors.initials: T
authors.lastname: Srivastava
authors.affiliation: Section of Cardiac Surgery, Children's Mercy Hospital and University of Missouri at Kansas City, Kansas City, MO 64108, USA.
authors.forename: Jos
authors.initials: J
authors.lastname: Domen
authors.affiliation: Department of Pharmacology, University of Montreal, Montreal, QC, Canada H3T 1J4.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Tormo
authors.affiliation: Department of Pharmacology, University of Montreal, Montreal, QC, Canada H3T 1J4.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Gauchat
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D001773:Blood Cells / Q000187:drug effects* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D053614:Janus Kinase 2 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D010766:Phosphorylation; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins; D013154:Spleen / Q000166:cytology
chemical_list: C000606074:CLCF1 protein, human; D016207:Cytokines; D015850:Interleukin-6; D011994:Recombinant Proteins; D053614:Janus Kinase 2