Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031099 (periodontitis)
 12,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aquaporin 3 (AQP3) is the predominant water channel protein in human keratinocytes and acts as an inflammatory mediator in some lesions. A chronic, inflammatory process of periodontitis is related with a dramatic change of surrounding fluid homeostasis to plasma extravasation. The exact pattern of aquaporin (AQP) water channel expression and its mechanism in periodontal disease is still unknown. We describe herein an up-regulated AQP3 expression in the epithelial lesion with chronic periodontitis and its functional role. The levels of AQP3 expression in inflamed gingival epithelial tissues were significantly higher than those of healthy subjects. Consistent with these results, AQP3 expression (i.e., levels of mRNA and protein) in cultured rat primary gingival epithelial cells and the human gingival epithelial cell line Ca9-22 were strongly increased in response to TNF-alpha treatment through the 55 kDa TNF-alpha receptor (TNFR I). In this context, small interfering RNA- (siRNA)-mediated "aqp-3 gene silencing," which could reduce AQP3 expression by more than 65%, significantly attenuated selected proinflammatory events of ICAM-1 expression induced by TNF-alpha in Ca9-22. A sixfold increase in leukocyte adherence to TNF-alpha-stimulated epithelial cells was demonstrated by an adherence assay (P < 0.001) and pretreatment with AQP3 siRNA and anti-ICAM-1 antibody reduced leukocyte retention by 85% (P < 0.001). Our study indicates for the first time a novel important mode in the regulation of the inflammatory response through TNF-alpha/TNFR I ligation at the site of epithelial lesions by specialized membrane channel AQP3 and ICAM-1 protein, which is closely implicated in the development of periodontitis mechanisms.
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PMID:The role of water channel aquaporin 3 in the mechanism of TNF-alpha-mediated proinflammatory events: Implication in periodontal inflammation. 1854 47

Aquaporins (AQPs) are membrane channels that provide for transport of water and other small molecules across the lipid bilayer of cells. Their function is essential for physiologic processes such as cell volume regulation, chondrocyte hypertrophy during appendicular skeletal growth, water reabsorption in the kidney tubules, and water excretion by the salivary glands. The ten AQP isoforms show tissue specificity and are involved in different pathologies and inflammatory diseases. This study addresses the hypothesis that arthritis, periodontitis, and temporomandibular joint disorders (TMDs) can be influenced by variation in the AQP genes at 12q13.12 locus. Salivary samples of 688 individuals were obtained from the Dental Registry and DNA Repository project at the University of Pittsburgh. Ten polymorphisms in four AQP genes (AQP1, 2, 5, and 6) were genotyped and correlated to disease status as reported by patients. Associations were found between the single nucleotide polymorphism (SNP) rs467323 in AQP2 and TMD in both genotypic (p = 0.03) and recessive (p = 0.02) models, and between rs1996315 in AQP6 and periodontitis (p = 0.05). Combined analysis of TMD and periodontitis showed an association with rs3741559 in AQP2 (p = 0.02). When conducting haplotype analysis of rs467323 and rs10875989 in AQP2, the haplotype CT showed an association with the TMD phenotype (p = 0.007). Our results suggest that the aquaporin locus at 12q13.12 may contribute to the pathogenesis of inflammatory conditions such as periodontitis and TMD. Thus, oral and skeletal health are correlated and potential susceptibility screening strategies may be developed.
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PMID:Aquaporin locus (12q13.12) might contribute to susceptibility of temporomandibular joint disorder associated with periodontitis. 3213 Feb 59