Impaired phosphorylation of JAK2-STAT5b signaling in fibroblasts from uremic children
Autor: | Maria L. Ceballos, Cristian Suazo, Jun Oh, Marta Azocar, Francisco Cano, Anne Katrin Dettmar, M. José Ibacache, Mauricio Lozano, Angela Delucchi, Iris Delgado, Carlos E. Irarrazabal, Francisca Ugarte, Gabriel Cavada, Angélica Rojo |
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Rok vydání: | 2016 |
Předmět: |
Male
0301 basic medicine Nephrology medicine.medical_specialty Biopsy Arbitrary unit Primary Cell Culture IGFBP3 030209 endocrinology & metabolism Stimulation 03 medical and health sciences 0302 clinical medicine Interquartile range Internal medicine STAT5 Transcription Factor medicine Humans Insulin-Like Growth Factor I Phosphorylation Renal Insufficiency Chronic Child Skin Uremia Human Growth Hormone business.industry Fibroblasts Janus Kinase 2 medicine.disease Actins Recombinant Proteins DNA-Binding Proteins Insulin-Like Growth Factor Binding Protein 3 030104 developmental biology Endocrinology Child Preschool Pediatrics Perinatology and Child Health STAT protein Female Carrier Proteins business Peritoneal Dialysis Signal Transduction Kidney disease |
Zdroj: | Pediatric Nephrology. 31:965-974 |
ISSN: | 1432-198X 0931-041X |
Popis: | Chronic kidney disease (CKD) in children is characterized by severe growth failure. The growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis in uremic animals shows a post-receptor impaired phosphorylation of Janus kinase 2/signal transducer and activator of transcription (JAK-STAT) proteins. The objective of our study was to characterize the intracellular phosphorylation of JAK-STAT signaling in fibroblasts from children with CKD on chronic peritoneal dialysis (PD). Serum GH-binding protein (GHBP), IGF-1 and IGFBP3 were measured in 15 prepubertal CKD stage-5 children on PD. Cytoplasmic JAK2, cytoplasmic/nuclear STAT5b and nuclear IGFBP3, acid-labile subunit (ALS) and IGF-1 mRNA expression were quantified in fibroblasts obtained from skin biopsies before and after stimulation with 200 ng/ml recombinant human growth hormone (rhGH). Phosphorylation activity at both the cytoplasmic and nuclear level was expressed as the ratio phosphorylated (p)/total (t) abundance of the product (p/t) at 30 and 60 min. Fifteen healthy children were recruited as the control group. Values were expressed in arbitrary units (AU) and normalized for comparison. Significance was defined as p |
Databáze: | OpenAIRE |
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