EGFR in Enamel Matrix Derivative-induced gingival fibroblast mitogenesis

Journal of Dental Research
E ZeldichM Weinreb

Abstract

We previously reported that EMD (Enamel Matrix Derivative) induces proliferation of human gingival fibroblasts via activation of Extracellular Regulated Kinase (ERK), and this study assessed the possible mediatory role of EGFR (Epidermal Growth Factor Receptor) in this effect. Treatment of gingival fibroblasts with EMD resulted in tyrosine phosphorylation of the EGFR, as assessed by immunoblotting and ELISA, while EMD-induced ERK activation and thymidine incorporation were markedly inhibited (approximately 40-50%) by a specific EGFR tyrosine kinase inhibitor. Using appropriate inhibitors, we established that EMD-induced EGFR activation is largely due to shedding of HB-EGF (Heparin-binding EGF) from the cell membrane via a metalloproteinase-mediated process. Finally, the addition of PP1, a Src family inhibitor, abrogated both EGFR phosphorylation and ERK activation. Taken together, these results indicate that, at least in human gingival fibroblasts, EMD-induced ERK activation and proliferation are partially due to a Src-dependent, metalloproteinase-mediated transactivation of EGFR.

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Dec 26, 2006·Journal of Dental Research·E ZeldichM Weinreb

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Citations

Nov 11, 2011·Tissue Engineering. Part B, Reviews·H Michelle GrandinMichel Dard
Mar 27, 2010·Journal of Oral Science·Matti LaaksonenTuula Salo
Apr 14, 2015·Periodontology 2000·Miron Weinreb, Carlos E Nemcovsky
Jul 15, 2015·Experimental and Therapeutic Medicine·Marzena Wyganowska-ŚwiątkowskaJerzy Jankun
Jan 19, 2016·Journal of Periodontology·Tal Maymon-GilMiron Weinreb
Nov 25, 2014·Journal of Periodontal Research·R J MironM Weinreb
Aug 14, 2015·Clinical Oral Investigations·Yulan WangRichard J Miron
Aug 11, 2011·PloS One·Inbal HechtEshel Ben-Jacob
Sep 20, 2019·BMC Oral Health·E OrlovaJ R Shaffer

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Datasets Mentioned

BETA
GM
6001

Methods Mentioned

BETA
Protein Assay
ELISA

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