title: Epiregulin can promote proliferation of stem cells from the dental apical papilla via MEK/Erk and JNK signalling pathways.
abstract: OBJECTIVE
  Mesenchymal stem cells (MSCs) are a reliable resource for tissue regeneration, but their molecular mechanisms of differentiation and proliferation remain unclear; this situation has restricted use of MSCs to a limited number of applications. A previous study of ours found a member of the epidermal growth factor family, epiregulin (EREG), to be involved in regulation of MSC differentiation. In the present study, we have used human dental stem cells from the apical papilla (SCAPs) to investigate the role of EREG on proliferation of MSCs.
  
  
  METHODS
  SCAPs were isolated from apical papillae of immature third molars. Retroviral short hairpin RNA (shRNA) was used to silence EREG gene expression, and human recombinant EREG protein was used to stimulate SCAPs. SCAP proliferation was examined using tetrazolium dye colorimetric assay/cell growth curve. Western blotting was performed to detect expressions of extracellular signal-regulated protein kinases 1 and 2 (Erk1/2), mitogen-activated protein kinases 1 and 2 (MEK1/2), protein kinase B (Akt), p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK).
  
  
  RESULTS
  Depletion of EREG with shRNA inhibited SCAP proliferation and repressed phosphorylation of Erk1/2 and JNK. Human recombinant EREG protein promoted cell proliferation and enhanced Erk1/2, MEK and JNK phosphorylation in SCAPs. Furthermore, blocking MEK/Erk signalling with specific Erk1/2 inhibitor PD98059, or JNK signalling with specific inhibitor SP600125, abolished effects of EREG on cell proliferation.
  
  
  CONCLUSIONS
  These findings indicate that EREG could enhance cell proliferation in dental tissue-derived MSCs by activating MEK/Erk and JNK signalling pathways.
authors.affiliation: Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100050, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Cao
authors.forename: D S
authors.initials: DS
authors.lastname: Xia
authors.forename: S R
authors.initials: SR
authors.lastname: Qi
authors.forename: J
authors.initials: J
authors.lastname: Du
authors.forename: P
authors.initials: P
authors.lastname: Ma
authors.forename: S L
authors.initials: SL
authors.lastname: Wang
authors.forename: Z P
authors.initials: ZP
authors.lastname: Fan
mesh_terms: D000293:Adolescent; D002454:Cell Differentiation / Q000502:physiology; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003771:Dental Papilla / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D004815:Epidermal Growth Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D066260:Epiregulin; D006801:Humans; D020935:MAP Kinase Signaling System; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C587880:EREG protein, human; D066260:Epiregulin; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases