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Nephrol Dial Transplant. 2014 Apr;29(4):791-9. doi: 10.1093/ndt/gfu003. Epub 2014 Jan 23.

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

Author information

1
Shraga Segal Department of Microbiology and Immunology, Ben Gurion University of the Negev, Beer Sheva, Israel.

Abstract

BACKGROUND:

Treatment 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.

METHODS:

Subtotal 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.

RESULTS:

Reduced 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.

CONCLUSIONS:

Despite 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.

KEYWORDS:

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

PMID:
24463190
DOI:
10.1093/ndt/gfu003
[Indexed for MEDLINE]
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