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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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
Issue number4
StatePublished - Apr 2014
Externally publishedYes


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


Dive into the research topics of 'Impaired renal growth hormone JAK/STAT5 signaling in chronic kidney disease'. Together they form a unique fingerprint.

Cite this