Differential gene and protein expression of tissue inhibitors of metalloproteinases (TIMP)-3 and TIMP-4 in gingival tissues from drug induced gingival overgrowth.
OBJECTIVE
The purpose of this study was to analyse mRNA expression and protein localization of tissue inhibitors of metalloproteinases (TIMP)-3 and TIMP-4 in gingival tissues removed from drug (calcium-channel blocker) induced gingival overgrowth and periodontitis patients.


METHODS
Employing RT-PCR, we evaluated TIMP-3 and TIMP-4 mRNA levels of 20 human gingival tissue samples taken from patients suffering gingival overgrowth (GO) and periodontitis (P). Then, using immunohistochemistry we investigated the TIMP-3 and TIMP-4 protein localization of five sample tissues from each group.


RESULTS
TIMP-4 mRNA levels in GO-gingiva tended to be lower than in P-gingiva but the results differed little (p = 0.22). Varying degrees of inflammation in the protein localization of TIMP-3 and TIMP-4 were found. TIMP-4 immunoreactivity (IR) was weak in the endothelial cells, fibroblasts, epithelial basal and parabasal cells while the degree of inflammation differed as well. TIMP-3 and TIMP-4 IR in inflammatory cells, including lymphocytes, plasma cells, and macrophages, were faint and intense respectively. For P-gingiva, both TIMP-3 and TIMP-4 IR expression was weak in the endothelial cells, fibroblasts, basal and parabasal epithelial layers. Expression of TIMP-3 was faint in the inflammatory cells, whereas TIMP-4 IR was strong.


CONCLUSIONS
Our findings suggest that TIMP-3 and TIMP-4 expression differs in GO and P-gingival tissues, both of which are potentially involved in pathogenesis.
Nakasone
Naohiro
N
Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata 951-8514, Japan. nakasone@dent.niigata-u.ac.jp
Kubota
Takehiko
T
Hoshino
Chika
C
Nohno
Kaname
K
Itagaki
Manami
M
Shimizu
Taro
T
Yoshie
Hiromasa
H
D000368:Aged; D002121:Calcium Channel Blockers / Q000009:adverse effects; D002467:Cell Nucleus / Q000201:enzymology; D003238:Connective Tissue / Q000201:enzymology; D003593:Cytoplasm / Q000201:enzymology; D042783:Endothelial Cells / Q000201:enzymology; D004847:Epithelial Cells / Q000201:enzymology; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D005881:Gingiva / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D019214:Gingival Overgrowth / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology; D008264:Macrophages / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D017622:Periodontal Attachment Loss / Q000201:enzymology; D010512:Periodontal Index; D010514:Periodontal Pocket / Q000201:enzymology; D010518:Periodontitis / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology; D010950:Plasma Cells / Q000201:enzymology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000032:analysis*; D019714:Tissue Inhibitor of Metalloproteinases / Q000032:analysis*; D000097792:Tissue Inhibitor of Metalloproteinase-4
D002121:Calcium Channel Blockers; D012333:RNA, Messenger; D019717:Tissue Inhibitor of Metalloproteinase-3; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4; C088390:TIMP3 protein, human