Impaired renal growth hormone JAK/STAT5 signaling in chronic kidney disease

Debbie Wiezel, Mohammed Hani Assadi, Daniel Landau, Ariel Troib, Leonid Kachko, Ralph Rabkin, Yael Segev

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

BackgroundTreatment with recombinant human growth hormone (GH) is the standard therapy for short stature in children with chronic kidney disease (CKD). However, concerns have been raised on the potential renal fibrogenic effects of GH. There is no information regarding the renal GH receptor (GHR)-JAK-STAT signaling pathway in CKD.MethodsSubtotal nephrectomized (CKD) and pair-fed sham-operated control (C) juvenile rats were treated with subcutaneous GH or saline for 2 weeks. A single intravenous GH bolus or vehicle was provided prior to euthanasia.ResultsReduced body weight in CKD was improved with GH therapy. The remnant kidney showed glomerular hypertrophy and early interstitial fibrosis without inflammatory infiltration. Treatment of CKD rats with GH did not worsen renal function or fibrosis. Kidney GHR mRNA and protein levels were reduced and basal phosphorylation of JAK2 and STAT5 was significantly impaired. However, intravenous GH administration prior to sacrifice normalized STAT5 phosphorylation. Basal renal IL6 mRNA and phosphorylation of its downstream signaling molecule STAT3 were increased as was the product of its action, the suppressor of cytokine signaling 3 (SOCS3) mRNA.ConclusionsDespite known unaltered circulating GH levels, remnant kidneys of uremic growth retarded juvenile rats show impaired basal signaling along the GH-activated JAK2/STAT5 signaling pathway. This may well be a consequence of the reduced GHR level and the inhibitory effect of the increase in IL-6-mediated SOCS3 expression. This renal GH insensitivity, if present in humans, may protect against the potential adverse renal effects of GH administration in CKD patients.

Original languageEnglish
Pages (from-to)791-799
Number of pages9
JournalNephrology Dialysis Transplantation
Volume29
Issue number4
DOIs
StatePublished - 1 Jan 2014

Keywords

  • IL-6
  • SOCS3
  • STAT5
  • chronic kidney disease
  • growth hormone

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