title: Gp130-dependent signaling in the podocyte.
abstract: Renal inflammation, in particular glomerular, is often characterized by increased IL-6 levels. The in vivo relevance of IL-6 signaling in glomerular podocytes, which play central roles in most glomerular diseases, is unknown. Here, we show that in normal mice, podocytes express gp130, the common signal-transducing receptor subunit of the IL-6 family of cytokines. Following systemic IL-6 or LPS injection in mice, podocyte IL-6 signaling was evidenced by downstream STAT3 phosphorylation. Next, we generated mice deficient for gp130 in podocytes. Expectedly, these mice exhibited abrogated IL-6 downstream signaling in podocytes. At the age of 40 wk, they did not show spontaneous renal pathology or abnormal renal function. The mice were then challenged using two LPS injury models as well as nephrotoxic serum to induce crescentic nephritis. Under all conditions, circulating IL-6 levels increased markedly and the mice developed the pathological hallmarks of the corresponding injury models such as proteinuria and development of glomerular crescents, respectively. However, despite the capacity of normal podocytes to transduce IL-6 family signals downstream, there were no significant differences between mice bearing the podocyte-specific gp130 deletion and their control littermates in any of these models. In conclusion, under the different conditions tested, gp130 signaling was not a critical component of the (patho-)biology of the podocyte in vivo.
authors.affiliation: Division of Nephrology and Immunology, RWTH Aachen University, Aachen Germany; Division of Nephrology, Showa University Fujigaoka Hospital, Yokohama, Japan.
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Nagayama
authors.affiliation: Division of Nephrology and Immunology, RWTH Aachen University, Aachen Germany; Institute of Biochemistry and Molecular Biology, RWTH Aachen University, Aachen, Germany; gbraun@ukaachen.de.
authors.forename: Gerald S
authors.initials: GS
authors.lastname: Braun
authors.affiliation: Division of Nephrology and Immunology, RWTH Aachen University, Aachen Germany;
authors.forename: Christina M
authors.initials: CM
authors.lastname: Jakobs
authors.affiliation: Division of Nephrology and Immunology, RWTH Aachen University, Aachen Germany; Division of Nephrology, Showa University Fujigaoka Hospital, Yokohama, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Maruta
authors.affiliation: Division of Nephrology and Immunology, RWTH Aachen University, Aachen Germany;
authors.forename: Claudia R
authors.initials: CR
authors.lastname: van Roeyen
authors.affiliation: Division of Nephrology and Immunology, RWTH Aachen University, Aachen Germany;
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Klinkhammer
authors.affiliation: Division of Nephrology and Immunology, RWTH Aachen University, Aachen Germany; Institute of Pathology, RWTH Aachen University, Aachen, Germany; Institute of Molecular Biomedicine, Comenius University, Bratislava, Slovakia; and.
authors.forename: Peter
authors.initials: P
authors.lastname: Boor
authors.affiliation: Division of Nephrology and Immunology, RWTH Aachen University, Aachen Germany;
authors.forename: Luigi
authors.initials: L
authors.lastname: Villa
authors.affiliation: Division of Nephrology and Immunology, RWTH Aachen University, Aachen Germany;
authors.forename: Ute
authors.initials: U
authors.lastname: Raffetseder
authors.affiliation: Division of Gastroenterology, Metabolic Diseases, and Intensive Care, RWTH Aachen University, Aachen, Germany;
authors.forename: Christian
authors.initials: C
authors.lastname: Trautwein
authors.affiliation: Institute of Biochemistry and Molecular Biology, RWTH Aachen University, Aachen, Germany;
authors.forename: Dieter
authors.initials: D
authors.lastname: Görtz
authors.affiliation: Institute of Biochemistry and Molecular Biology, RWTH Aachen University, Aachen, Germany;
authors.forename: Gerhard
authors.initials: G
authors.lastname: Müller-Newen
authors.affiliation: Division of Nephrology and Immunology, RWTH Aachen University, Aachen Germany;
authors.forename: Tammo
authors.initials: T
authors.lastname: Ostendorf
authors.affiliation: Division of Nephrology and Immunology, RWTH Aachen University, Aachen Germany;
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000009:adverse effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009393:Nephritis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D006023:Glycoproteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D050822:Cytokine Receptor gp130
keywords: crescentic nephritis; glomerulus; gp130; lipopolysaccharide; pSTAT3