Hepatocyte growth factor (HGF) system in gingiva: HGF activator expression by gingival epithelial cells.
Hepatocyte growth factor (HGF) acts as a mitogen, motogen, morphogen, and anti-apoptotic factor for various kinds of epithelial cells. We previously showed that periodontal ligament and gingival fibroblasts secreted an HGF-like chemoattractant for a gingival epithelial cell line and found that the HGF content of gingival crevicular fluid was well correlated with clinical parameters and interleukin-1beta level. Since HGF is secreted as an inactive form (proHGF), and converted to an active form by serine proteases such as HGF activator (HGFA), extracellular processing of proHGF is presumed to be critical in the regulation of HGF activity. To examine the role of the HGF system in epithelial invasion followed by loss of connective tissue attachment in periodontitis, mRNA expression of HGF, its receptor (c-met) and HGFA in gingival tissues was monitored. Ten gingival biopsies were obtained, and epithelium and connective tissues were separated by enzymatic digestion. The gene expression of HGF and keratinocyte growth factor (KGF) in gingival connective tissue, and c-met, HGFA and KGF receptor (KGFR) in gingival epithelial tissues was monitored using RT-PCR. Furthermore, HGFA protein in the conditioned medium of cultured primary gingival epithelial cells was examined using Western blotting. All the connective tissue samples expressed KGF, and 8 out of 10 samples expressed HGF. All the epithelial samples expressed KGFR and c-met, whereas 5 out of 10 samples expressed HGFA. Protein expression of HGFA by cultured primary gingival epithelial cells was also confirmed. In terms of local production and activation of HGF in gingival tissue, these results suggest that synergistic expression of HGF in connective tissue and HGFA expression in epithelium may contribute to disease progression in periodontitis.
Ohshima
Mitsuhiro
M
Department of Biochemistry, Nihon University School of Dentistry, Tokyo 101-8310, Japan. oshima-m@dent.nihon-u.ac.jp
Sakai
Akihiko
A
Sawamoto
Yoshihiro
Y
Seki
Keisuke
K
Ito
Koichi
K
Otsuka
Kichibee
K
D001706:Biopsy; D015153:Blotting, Western; D002478:Cells, Cultured; D003238:Connective Tissue / Q000378:metabolism; D017077:Culture Media, Conditioned; D004591:Electrophoresis, Polyacrylamide Gel; D004847:Epithelial Cells / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D005881:Gingiva / Q000166:cytology / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D017622:Periodontal Attachment Loss / Q000378:metabolism; D010518:Periodontitis / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*
D017077:Culture Media, Conditioned; C496453:FGF7 protein, human; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D051497:Receptor, Fibroblast Growth Factor, Type 2; C065104:keratinocyte growth factor receptor; C081092:HGF activator; D012697:Serine Endopeptidases