Annals of Pediatric Endocrinology and Metabolism

  • 제23권4호
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  • Pages.204-209
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  • 2018
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  • 2287-1012(pISSN)
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  • 2287-1292(eISSN)
대한소아내분비학회 (Korean Society of Pediatric Endocrinology)
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The role of p21/CIP1/WAF1 (p21) in the negative regulation of the growth hormone/growth hormone receptor and epidermal growth factor/epidermal growth factor receptor pathways, in growth hormone transduction defect

  • Kostopoulou, Eirini (Paediatric Endocrine Research Laboratory, Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics, University of Patras School of Medicine) ;
  • Gil, Andrea Paola Rojas (Faculty of Human Movement and Quality of Life Sciences, Department of Nursing, University of Peloponnese) ;
  • Spiliotis, Bessie E. (Paediatric Endocrine Research Laboratory, Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics, University of Patras School of Medicine)
  • 투고 : 2018.03.18
  • 심사 : 2018.10.17
  • 발행 : 2018.12.30
⟨ 이전 논문 다음 논문 ⟩

초록

Purpose: Growth hormone transduction defect (GHTD) is characterized by severe short stature, impaired STAT3 (signal transducer and activator of transcription-3) phosphorylation and overexpression of the cytokine inducible SH2 containing protein (CIS) and p21/CIP1/WAF1. To investigate the role of p21/CIP1/WAF1 in the negative regulation of the growth hormone (GH)/GH receptor and Epidermal Growth Factor (EGF)/EGF Receptor pathways in GHTD. Methods: Fibroblast cultures were developed from gingival biopsies of 1 GHTD patient and 1 control. The protein expression and the cellular localization of p21/CIP1/WAF1 was studied by Western immunoblotting and immunofluorescence, respectively: at the basal state and after induction with $200-{\mu}g/L$ human GH (hGH) (GH200), either with or without siRNA CIS (siCIS); at the basal state and after inductions with $200-{\mu}g/L$ hGH (GH200), $1,000-{\mu}g/L$ hGH (GH1000) or 50-ng/mL EGF. Results: After GH200/siCIS, the protein expression and nuclear localization of p21 were reduced in the patient. After successful induction of GH signaling (control, GH200; patient, GH1000), the protein expression and nuclear localization of p21 were reduced. After induction with EGF, p21 translocated to the cytoplasm in the control, whereas in the GHTD patient it remained located in the nucleus. Conclusion: In the GHTD fibroblasts, when CIS is reduced, either after siCIS or after a higher dose of hGH (GH1000), p21's antiproliferative effect (nuclear localization) is also reduced and GH signaling is activated. There also appears to be a positive relationship between the 2 inhibitors of GH signaling, CIS and p21. Finally, in GHTD, p21 seems to participate in the regulation of both the GH and EGF/EGFR pathways, depending upon its cellular location.

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참고문헌

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