Premium
Anti‐TGF‐β antibody blocks enamel matrix derivative‐induced upregulation of p21 WAF1/cip1 and prevents its inhibition of human oral epithelial cell proliferation
Author(s) -
Kawase Tomoyuki,
Okuda Kazuhiro,
Yoshie Hiromasa,
Burns Douglas M.
Publication year - 2002
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1034/j.1600-0765.2002.01615.x
Subject(s) - enamel matrix derivative , transforming growth factor beta , phosphorylation , cell growth , neutralizing antibody , transforming growth factor , microbiology and biotechnology , signal transduction , kinase , p38 mitogen activated protein kinases , cell culture , biology , chemistry , cancer research , antibody , protein kinase a , biochemistry , immunology , genetics , regeneration (biology)
We have previously demonstrated that porcine enamel matrix derivative (EMD) contains TGF‐β1 (or a TGF‐β‐like substance), and that EMD rapidly translocates smad2, which is an effector of the TGF‐β signaling pathway, into the nucleus and modulates the proliferation of both human gingival fibroblastic and oral epithelial cells in a cell type‐specific manner. To investigate the involvement of TGF‐β in the growth modulatory action of EMD, two approaches have been used in the present study: i) a neutralizing anti‐TGF‐β antibody to block EMD action, and ii) authentic porcine TGF‐β1 to compare with EMD. Both in epithelial and fibroblastic cells, TGF‐β1 closely mimicked EMD in nuclear accumulation of smad2, phosphorylation of MAP kinase family members, and consequent cell type‐specific growth modulation. Anti‐TGF‐β antibody, at levels which completely blocked TGF‐β1‐induced smad2 translocation, strongly blocked EMD‐induced smad2 translocation. This antibody also blocked other actions of EMD in epithelial cells, i.e. p38‐MAP kinase (p38‐K) phosphorylation, p21 WAF1/cip1 expression, and inhibition of DNA synthesis . In support of our previousproposal,thesedatasuggest that TGF‐β1 (or a TGF‐β‐like substance), which is delivered as a principal bio‐active factor in EMD, inhibits epithelial cell proliferation probably by a smad2‐mediated, p21 WAF1/cip1 ‐dependent mechanism. However, the same neutralizing antibody failed to convincingly block EMD‐induced fibroblastic proliferation, which suggests that EMD may contain additional unidentified mitogenic factor(s), which act in combination with TGF‐β to fully stimulate fibroblastic proliferation.