Open AccessEpiregulin can promote proliferation of stem cells from the dental apical papilla via MEK/Erk and JNK signalling pathways
Author(s) -
Cao Y.,
Xia D. S.,
Qi S. R.,
Du J.,
Ma P.,
Wang S. L.,
Fan Z. P.
Publication year - 2013
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12039
Subject(s) - epiregulin , mapk/erk pathway , microbiology and biotechnology , cell growth , kinase , protein kinase a , protein kinase b , biology , p38 mitogen activated protein kinases , signal transduction , chemistry , epidermal growth factor , receptor , biochemistry , amphiregulin
Objectives Mesenchymal stem cells ( MSC s) are a reliable resource for tissue regeneration, but their molecular mechanisms of differentiation and proliferation remain unclear; this situation has restricted use of MSC s 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 ( SCAP s) to investigate the role of EREG on proliferation of MSC s. Materials and methods SCAP s were isolated from apical papillae of immature third molars. Retroviral short hairpin RNA (sh RNA ) was used to silence EREG gene expression, and human recombinant EREG protein was used to stimulate SCAP s. 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 ( MEK 1/2), protein kinase B (Akt), p38 mitogen‐activated protein kinase (p38 MAPK ) and c‐Jun N‐terminal kinase ( JNK ). Results Depletion of EREG with sh RNA 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 SCAP s. 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. Conclusion These findings indicate that EREG could enhance cell proliferation in dental tissue‐derived MSC s by activating MEK/Erk and JNK signalling pathways.