Liver growth hormone receptor signaling in chronic kidney disease related growth retardation: the role of suppressor of cytokine signaling 2

Rawan Hilal, Mohammad Assadi, Yu Chen, Julio Medrano, Ralph Rabkin, Yael Segev, Daniel Landau

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Children with chronic kidney disease (CKD) who suffer from growth retardation have usually normal circulating GH but low IGF1, suggesting GH resistance. We have previously shown in growth retarded CKD rats an increase in suppressor of cytokine signaling 2 (SOCS2) levels, a key negative regulator of GH signaling. SOCS2 spontaneously mutated (HG) mice show an exaggerated body growth and increased bone mass. We investigated growth and GH receptor (GHR) signaling in liver tissue of uremic SOCS2 deficient mice.

Methods: 4-week old HG and normal wild-type mice (N) underwent 5/6 nephrectomy (CKD) or sham operation (C), forming four groups: C-N, C-HG, CKD-N, CKD-HG. Mice were sacrificed after 3 weeks (3W) or 12 weeks (12W) after disease induction. A single IP bolus of bovine GH was given 30 min before sacrifice.
Results: CKD-N and CKD-HG mice had similar degrees of renal insufficiency. Weight gain was reduced significantly in CKD-N vs C-N, but increased significantly in C-HG & CKD-HG. Liver SOCS2 mRNA, totally absent in HG mice, was increased in CKD-N vs C-N. Liver GHR protein levels were similar in all groups, excluding an elevation in the C-HG group after 12W. GH stimulated STAT5 phosphorylation decreased in CKD-N vs C-N in both time points and increased in CKD-HG vs CKD-N only after 3W but not after 12W. IL6 and SOCS3 mRNA, and phospho-STAT3 (a signal downstream of IL6) increased in CKD-HG after 3W. Phospho-STAT3 increased in C-HG, CKD-N and CKD-HG vs C-N further increasing in C-HG. SOCS3 increased in CKD-N and IL6 increased in CKD-HG, further increasing in C-HG after 12W.
Original languageEnglish
Pages (from-to)81
JournalBone Abstracts
Volume4
DOIs
StatePublished - 9 Jun 2015

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