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
Rok vydání: 2016
Předmět:
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