CD147and Caveolin-1in Oral Disease

Oral cavity is the start of a digestive tube, and interlinked with respiratory tract, at the same time, neighbouring brain, which have the function of chewing, swallowing and speech. Oral diseases often affects people’s quality of life and even threaten the life, has been more and more get people’s attention. Periodontitis is a common disease, which affected by multiple factors of chronic inflammatory diseases. Periodontitis pathological characteristics included the destruction of the alveolar bone and the extracellular matrix (extracellular matrix, ECM) degradation. Oral squamous cell carcinoma is a common malignant tumor, higher incidence and accompanied by the growth of the age has a tendency to rise. Degradation of ECM and basement membrane is the key step in the oral epithelial hyperplasia and cancer. Matrix metalloproteinases (MMPs), is a set of Zn2+depend on endogenous peptide enzyme, which plays an important role in the process of ECM degradation. A large number of studies have shown that MMPs play an important role in periodontal tissue pathological physiological conditions.Extracellular matrix metalloproteinases inducing factor (CD147) is a kind of cell surface transmembrane glycoprotein, also called CD147, belongs to the immunoglobulin superfamily member. One of the most important function about CD147is to induce the production of MMPs, which involved in many physiological and pathological development process. We found that the host factors about CD147-MMPs-periodontitis axis, and the axis is associated with the degree of periodontal inflammation. there may be a link between for host factors involved in pathogenic provides another evidence of periodontitis. At the same time multiple studies confirm CD147is associated with inflammation, hyperplasia, precancerous lesions and cancer.CD147is composed of two extracellular immunoglobulin (Ig) domains. The first CD147Ig domain is associated with MMPs induction and the second is involved in Caveolin-1. The extracellular region of CD147contains three N-glycosylation sites, which contribute to both high glycoforms (HG-CD147) and low glycoforms (LG-CD147). HG-CD147(but not LG-CD147) can be self-clustering and CD147-dependent MMP-1-induction.Caveolae are invaginations in the plasma membrane, which are about50-100nm specificity invagination, participating in a variety of cell life activities. Caveolin-1is an important structural protein of caveolae, mainly expressed in the epithelial cells, endothelial cells, fibroblasts, fat cells, muscle cells, etc. Caveolin-1participates in intracellular molecules transportation and signal transmission. Caveolin-1is associated with CD147, which blocks CD147glycosylation, self-clustering and CD147-dependent MMP-1-induction. At the same time, the study also found that caveolin-1can inhibit the expression of MMPs, number of studies speculated that it is because of caveolin-1inhibit CD147glycosylation.No reports on the possible about caveolin-1in the periodontal tissue as well as drug induced golden gophers cheek pouch normal epithelium simple hyperplasia to dysplasia hyperplasia and then squamous cell carcinoma of the process are available. Moreover, whether caveolin-1is associated with CD147glycosylation in periodontitis and oral squamous cell carcinoma remains unknown.Experiment1investigated CD147glycosylation and Caveolin-1expression as well as the co-localization in healthy and inflamed human gingival tissues, analyzed the relationship between Caveolin-1and CD147, and resulting in influence of MMPs. Experiment2explore CAV1single nucleotide polymorphism is related to the susceptibility of periodontitis. Experiment3explored the relationship between CD147and caveolin-1, and resulting in influence of MMPs in the process of oral epithelial tissue lesions.EXPERIMENT1Expression of CD147glycosylation and Caveolin-1in healthy and inflamed human gingivaObjective:This study investigated the expression of Caveolin-1in healthy and inflamed human gingival tissues, analyzed the relationship between Caveolin-1and CD147, and resulting in influence of MMPs.Material and Methods:Gingival tissues were collected from10healthy subjects and15subjects with chronic periodontitis (CP). Caveolin-1, CD147, MMP-1, MMP-8and MMP-13expressions were assayed by immunohistochemistry and Western blot. Co-localization of Caveolin-1and CD147was detected by immunofluorescence.Results:Strong Caveolin-1immunoreactivity was detected in gingival epithelium and endothelial cells. CD147was expressed in gingival epithelium and evidently in inflammatory, endothelial and fibroblast-like cells under inflammatory conditions. Double immunofluorescence studies revealed the co-localization of Caveolin-1and CD147in gingival epithelium, endothelial and fibroblast-like cells. Strong immunoreactivity of MMP-8was observed in neutrophils, and MMP-13was observed in round-shaped monocytes. Compared with healthy subjects, the CP group had higher expression levels of HG-CD147, active MMP-1, proMMP-8and proMMP-13(p<0.05). The protein levels of active MMP-1, proMMP-1and MMP-13were positively correlated with that of HG-CD147(p<0.05).Conclusion:CD147-caveolin-1interaction may exist in periodontal physiological and pathological processes. The increased production of active MMP-1, proMMP-1and MMP-13may be associated with elevated HG-CD147levels.EXPERIMENT2Association of CAV1single nucleotide polymorphisms with severe peridontitisObjective:This study investigated the potential association of tagging single nucleotide polymorphisms (SNPs) of CAV1with severe periodontitis in a Chinese population.Material and methods:128patients with severe periodontitis and113control subjects with no to mild periodontitis were analyzed for common variants in BSG using a SNPs tagging approach. SNPbrowser4.0(Applied Biosystems, FosterCity, CA, USA) was used to SNPs selection of CAV1gene:rs3779512, rs3807986, rs4730751, rs3807989, rs729949, rs1049337. Six tagging SNPs were genotyped using matrix-assisted laser desorption ionization time of flight mass spectrometry (iPLEX MassARRAY system). Allele distribution of SNP in case and control group was analysed using genotypic test, allelic test, dominant gene action test and recessive gene action test. HAPLO-VIEW3.32software was used to detect haplotype blocks in six SNPs site.Results:Polymorphisms of the genotyped SNPs:rs3779512, rs3807986, rs4730751, rs3807989, rs729949å'Œrs1049337existed in Chinese people. Polymorphisms of them were T/G, G/A, A/C, A/G, A/G and C/T, minor allele frequencies were7.84%,22.65%,0.90%,27.97%,20.89%,45.74%consecutively. Allele distributions of rs3779512, rs3807986, rs4730751, rs3807989, rs729949and rs1049337between case and control group were no statistically significant in genotypic test, allelic test, dominant gene action test or recessive gene action test. One haplotype block including rs3807989, rs729949and rs1049337was detected. x2test of haplotype allele distribution between case and control group showed statistical insignificant.Conclusion:The tagging SNPs of the CAV1gene may be not associated with the susceptibility to severe periodontitis among Chinese population. Experiment3The relationship between CD147and caveolin-1in oral squamous cell carcinomaObjective:To investigate the expression and role of Caveolin-1and CD147in the pathogenesis of epithelial tissue lesions.Material and methods:Fifty6-8week-old male Syrian golden hamsters were divided into four experimental and one control groups (10animals in each groups).Both left pouches of each animal in the experimental groups were painted with0.5%DMBA solution, then killed0,4,8,10and13weeks. The control group remained untreated throughout the experiment. Caveolin-1and CD147expressions were assayed by immunohistochemistry and Western blot. MMP-2and MMP-9expressions were assayed by gelatin zymography.Results:The epithelium transformed malignancy gradually in normal, hyperplasia, slight dysplasia, severe dysplasia and carcinoma. The expression of CD147showed a increase of expression from baseline to13week(p<0.05), Immunohistochemistry showed that CD147in healthy epithelial tissue were negative or weakly positive staining, following the epithelial tissue pathological changes aggravated, the expression of CD147significantly enhanced. By contrast, caveolin-1in healthy epithelial tissue is strong positive staining, following the deterioration of the epithelial tissue pathological changes, caveolin-1expression significantly reduced. Western blot and gelatin enzyme spectrum detection showed that CD147, MMP-2and MMP-9protein expression level increased gradually, and the protein expression level of caveolin-1gradually reduced. CD147and negatively correlated with the protein expression level of caveolin-1. MMP-2and MMP-9had a strong and positive correlation with CD147, and a negatively correlated with caveolin-1protein expression level.Conclusion:CD147and caveolin-1expression on the epithelial cell membrane, and there is almost the opposite mode of expression, speculated that the interaction of CD147and caveolin-1may exist in oral epithelial lesions of different pathological period. The level of expression of caveolin-1is negative associated with the expression of CD147, MMP-2and MMP-9.In conclusion, the experiment1distinguished various CD147glycoforms in the periodontal tissue, also found that CD147and caveolin-1were mainly co-located in gingival epithelial cells, endothelial cells and gingival fibroblasts. CD147and caveolin-1possible interactions in the pathological process of periodontitis. Increased active MMP-1, proMMP-1and proMMP-13production may be associated with increase in HG-CD147level. Experiments2explore the relationship between CAV1SNPs and the susceptibility to severe periodontitis. Based on the results of the experiment1, experiments3confirmed that the interaction of CD147and caveolin-1is likely to exist in oral epithelial tissue of physiological and pathological process, and then influence the expression of MMPs. These three experiments try to explore the relationship between CD147and caveolin-1, and study the relationship between them and periodontitis. In order to improve the CD147-MMPs-periodontitis axis...