Epidermal growth factor receptor (EGFR) involvement in successful growth hormone (GH) signaling in GH transduction defect

Autor: Alexia Karvela, Bessie E. Spiliotis, Eirini Kostopoulou, Andrea Paola Rojas-Gil
Rok vydání: 2017
Předmět:
Male
STAT3 Transcription Factor
0301 basic medicine
medicine.medical_specialty
Endocrinology
Diabetes and Metabolism
Immunoblotting
Fluorescent Antibody Technique
Suppressor of Cytokine Signaling Proteins
030209 endocrinology & metabolism
Growth hormone receptor
03 medical and health sciences
0302 clinical medicine
Endocrinology
Growth factor receptor
Epidermal growth factor
Internal medicine
medicine
Humans
Immunoprecipitation
Growth factor receptor inhibitor
Epidermal growth factor receptor
Phosphorylation
Child
STAT3
Receptor
Growth Disorders
Cellular localization
Epidermal Growth Factor
biology
Human Growth Hormone
business.industry
Receptors
Somatotropin
Fibroblasts
Prognosis
ErbB Receptors
030104 developmental biology
Case-Control Studies
Pediatrics
Perinatology and Child Health
biology.protein
Female
business
Biomarkers
hormones
hormone substitutes
and hormone antagonists
Follow-Up Studies
Zdroj: Journal of Pediatric Endocrinology and Metabolism. 30
ISSN: 2191-0251
0334-018X
DOI: 10.1515/jpem-2016-0189
Popis: Background:Growth hormone (GH) transduction defect (GHTD) is a growth disorder with impaired signal transducer and activator of transcription 3 (STAT3) phosphorylation mediated by overexpression of cytokine-inducible SH2-containing protein (CIS), which causes increased growth hormone receptor (GHR) degradation. This study investigated the role of epidermal growth factor (EGF) in the restoration of normal GH signaling in GHTD.Methods:Protein expression, cellular localization and physical contact of proteins of the GH and EGF signaling pathways were studied by Western immunoblotting, immunofluorescence and co-immunoprecipitation, respectively. These were performed in fibroblasts of one GHTD patient (P) and one control child (C) at the basal state and after induction with human GH (hGH) 200 μg/L (GH200), either with or without silencing of CIS mRNA, and after induction with hGH 1000 μg/L (GH1000) or 50 ng/mL EGF.Results:The membrane availability of the EGF receptor (EGFR) and the activated EGFR (pEGFR) was increased in P only after simultaneous GH200 and silencing of CIS mRNA or with GH1000, whereas this occurred in C after GH200 alone. After EGF induction, the membrane localization of GHR, STAT3 and that of EGFR were increased in P more than in C.Conclusions:In conclusion, in GHTD, the EGFR seems to participate in successful GH signaling, but induction of GHTD fibroblasts with a higher dose of hGH is needed. The EGF/EGFR pathway, in contrast to the GH/GHR pathway, seems to function normally in P and is more primed compared to C. The involvement of the EGFR in successful GH signaling may explain the catch-up growth seen in the Ps when exogenous hGH is administered.
Databáze: OpenAIRE
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