title: IL-6 signaling in diabetic nephropathy: From pathophysiology to therapeutic perspectives.
abstract: Diabetic nephropathy (DN) is a leading cause of chronic kidney disease (CKD). Interleukin-6 (IL-6) signaling participates in inflammation responses central to the progression of DN. Current evidence suggests that these IL-6 responses are mediated via gp130-STAT3 dependent mechanisms which, on one hand, trigger globally the transition from innate to adaptive immune response, and on the other hand act locally for tissue remodeling and immune cell infiltration. In diabetic conditions the role of IL-6 is not well elucidated. Both IL-6 classical signaling pathway via receptor IL-6R (IL-6R) and IL-6 trans-signaling pathway via soluble IL-6R (sIL-6R) were shown to participate in the pathogenesis and progression of DN, and IL-6 appears to influence renal cells also in an autocrine manner. To date, evidence is limited. The goal of this review is to provide an overview of our current understanding on the role of IL-6 signaling in DN and to delineate challenges for future research. Putative sequential events related to IL-6 secretion by different cell populations in diabetic conditions are outlined. Further, we discuss potential applications of anti-IL-6 therapy in the context of DN.
authors.affiliation: CHU de Poitiers, Service d'Endocrinologie, Pole DUNE, Poitiers, France; Université de Poitiers, UFR Médecine Pharmacie, Poitiers, France; INSERM, CIC 1402 & U1082, University of Poitiers, France. Electronic address: eva.feigerlova@fulbrightmail.org.
authors.forename: Eva
authors.initials: E
authors.lastname: Feigerlová
authors.affiliation: INSERM U954, Nutrition Génétique et Exposition aux Risques Environnementaux, Medical Faculty, University of Lorraine and Regional University Hospital Center of Nancy, Vandœuvre les Nancy, France.
authors.forename: Shyue-Fang
authors.initials: SF
authors.lastname: Battaglia-Hsu
mesh_terms: D000818:Animals; D050822:Cytokine Receptor gp130 / Q000235:genetics / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy*; D018450:Disease Progression; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C508600:IL6 protein, human; C494199:IL6ST protein, human; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; D050822:Cytokine Receptor gp130
keywords: Diabetic nephropathy; IL-6 signaling; Immunoregulation; Trans-signaling