Skin characteristics associated with foot callus in people with diabetes: A cross-sectional study focused on desmocollin1 in corneocytes.

AIM: The purpose of this study was to investigate the degradation of desmocollin-1 (DSC1), a member of the desmosomal cadherin family in patients with diabetes, as well as the factors associated with the suppression of DSC1 degradation. METHODS: This cross-sectional study included 60 cases of foot callus involving 30 patients with diabetes (DM) and 30 matched volunteers without diabetes (non-DM). DSC1 degradation in samples from debrided calluses was analysed using western blotting. Skin hydration, a factor reported to suppress DSC1 degradation, was measured using a mobile moisture device. RESULTS: Full-length DSC1 (approximately 100 kDa) was detected in six participants only in the DM group, and no relationship was found between the suppression of DSC1 degradation and decreased skin hydration in the DM group. There was no significant difference in skin hydration values between the DM and non-DM groups. CONCLUSION: DSC1 degradation was suppressed in the DM group. There was no relationship between the suppression of DSC1 degradation and decreased skin hydration in the DM group. Current external force callus care would not be sufficient. This study highlights the need to develop novel callus care to enhance the degradation of DSC1.

The p53 target gene desmocollin 3 acts as a novel tumor suppressor through inhibiting EGFR/ERK pathway in human lung cancer.

Desmosomes are intercellular junctions that confer strong cell-cell adhesion. Altered expression of desmocollin 3 (DSC3), a member of the desmosomal cadherin family, was found in various cancers; however, its functional involvement in carcinogenesis has not yet been elucidated. Expression/localization of DSC3 was analyzed by real-time reverse transcription-PCR, western blotting, immunofluorescence and immunohistochemistry. Methylation status of DSC3 was examined by demethylation tests, methylation-specific PCR and bisulfite sequencing. It turned out that downregulation of DSC3 in lung cancer cells was associated with DNA hypermethylation. In primary lung tumors, DSC3 was a potential diagnostic marker for lung squamous cell carcinoma, and DSC3 DNA hypermethylation was correlated with poor clinical outcome. To investigate the effect of the tumor suppressor gene p53 on DSC3, transient transfection with a wild-type p53-expression vector was performed. Overexpression of p53 resulted in an increased expression of DSC3 in a DSC3-unmethylated lung cancer cell line H2170, but not in H1299, a DSC3-methylated cell line. However, combination of p53 transfection with demethylation agent 5-aza-2'-deoxycytidine treatment led to increased expression of DSC3 in H1299 cells. Furthermore, functional studies after stable transfection of a DSC3 expression vector showed that ectopic expression of DSC3 inhibited cell proliferation, anchorage-independent growth, migration, as well as invasion, and most interestingly led to reduced phosphorylation levels of extracellular signal-regulated kinase1/2. Taken together, our data suggested that DSC3 acts as a novel tumor suppressor gene through inhibition of epidermal growth factor receptor/extracellular signal-regulated kinase signaling in lung cancer cells.

Desmocollin 2 is a new immunohistochemical marker indicative of squamous differentiation in urothelial carcinoma.

AIMS: Urothelial carcinoma (UC) with squamous differentiation tends to present at higher stages than pure UC. To distinguish UC with squamous differentiation from pure UC, a sensitive and specific marker is needed. Desmocollin 2 (DSC2) is a protein localized in desmosomal junctions of stratified epithelium, but little is known about its biological significance in bladder cancer. We examined the utility of DSC2 as a diagnostic marker. METHODS AND RESULTS: We analysed the immunohistochemical characteristics of DSC2, and studied the relationship of DSC2 expression with the expression of the known markers uroplakin III (UPIII), cytokeratin (CK)7, CK20, epidermal growth factor receptor (EGFR), and p53. DSC2 staining was detected in 24 of 25 (96%) cases of UC with squamous differentiation, but in none of 85 (0%) cases of pure UC. DSC2 staining was detected only in areas of squamous differentiation. DSC2 expression was mutually exclusive of UPIII expression, and was correlated with EGFR expression. Furthermore, DSC2 expression was correlated with higher stage (P = 0.0314) and poor prognosis (P = 0.0477). CONCLUSIONS: DSC2 staining offers high sensitivity (96%) and high specificity (100%) for the detection of squamous differentiation in UC. DSC2 is a useful immunohistochemical marker for separation of UC with squamous differentiation from pure UC.

Expressions of Thyroid Transcription Factor-1, Napsin A, p40, p63, CK5/6 and Desmocollin-3 in Non-Small Cell Lung Cancer, as Revealed by Imprint Cytology Using a Malinol-Based Cell-Transfer Technique.

BACKGROUND: The introduction of new therapies has made it important to differentiate between adenocarcinoma and squamous cell carcinoma. To allow the use of various immunocytochemical stains on limited materials, we tried transferring cells from a given smear to multiple slides. Using touch-preparation samples of 215 surgically resected non-small cell lung carcinomas of confirmed histologic classification (adenocarcinoma,n = 101; squamous cell carcinoma,n = 114), we performed immunocytochemistry for thyroid transcription factor-1, napsin A, p40, p63, CK5/6 and desmocollin-3, and compared cytologic staining results with the corresponding resection. METHODS: We examined: (a) the expressions of the above 6 antibodies on cells transferred from touch imprints of resected specimens, the extent of staining being considered positive if more than 5% of the area was stained, and (b) the sensitivity, specificity, positive predictive value and negative predictive value for each antibody. RESULTS: The histologic corresponding rate with Papanicolaou staining was only 73%. Regarding the differentiation of adenocarcinoma from squamous cell carcinoma, the sensitivity and specificity for napsin A in adenocarcinoma were 80 and 97%, respectively, while those for p40 in squamous cell carcinoma were 84 and 98%, respectively. CONCLUSION: The immunocytochemical expressions of napsin A and p40 in imprint cytology seem to be of great utility for the accurate histological differentiation of lung cancers.

Differential phenotype of intervertebral disc cells: microarray and immunohistochemical analysis of canine nucleus pulposus and anulus fibrosus.

STUDY DESIGN: Microarray gene expression profiling, quantitative gene expression analysis, and immunohistochemistry was used to investigate molecular variations between nucleus pulposus (NP) and anulus fibrosus (AF) of the dog intervertebral disc (IVD). OBJECTIVE: To identify specific molecules with differing expression patterns in NP and AF and compare their profile with articular cartilage (AC). SUMMARY OF BACKGROUND DATA: Although experimental and animal studies have demonstrated the potential of cell based approaches for NP regeneration, there is still a deficiency of basic knowledge about the phenotype of IVD cells. METHODS: Comparative microarray analysis of beagle lumbar NP and AF was performed. Molecules of interest were evaluated by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry, comparing lumbar and coccygeal NP and AF and AC. To assess interspecies variations, genes that had been found differentially expressed in rat tissues were also investigated. RESULTS: Forty-five genes with NP/AF signal log ratio > or = 1 were identified. Alpha-2-macroglobulin, cytokeratin-18, and neural cell adhesion molecule (CD56) mRNA were higher in NP compared to AF and AC, and desmocollin-2 mRNA was higher in NP than AF. The expression profiles were similar in lumbar and coccygeal discs, although certain variations were noticed. Interspecies differences between rat and dog were evident in the expression of several genes. Immunohistochemistry confirmed differences in gene expression at the protein level. CONCLUSION: This study reports on the expression of molecules that have not been described previously in IVD, in non-notochordal discs comparable with human. Interspecies differences were noted between rat and dog tissues, whereas variations between caudal and lumbar discs were less prominent. The NP of the beagle as a chondrodystrophoid dog breed is potentially more similar to the human than the NP of species whose discs do not naturally degenerate. Therefore, studies on appropriate species may contribute to a better understanding of the cell types residing in the IVD.

Desmosomes are unaltered during infections by attaching and effacing pathogens.

The human attaching and effacing (A/E) intestinal pathogens enterohemorrhagic Escherichia coli (EHEC), enteropathogenic E. coli (EPEC), and the murine A/E pathogen Citrobacter rodentium cause serious diarrhea in their hosts. These bacteria alter numerous host cell components, including organelles, the host cell cytoskeleton, and tight junctions during the infectious process. One of the proteins that contribute to the intermediate filament network in host cells, cytokeratin-18, is extensively altered during EPEC infections. Based on this, we tested the hypothesis that desmosomes, the only intercellular junctions that interact with intermediate filaments, are also influenced by A/E pathogen infections. We found that the desmosomal transmembrane proteins desmoglein and desmocollin, as well as the desmosome plaque protein desmoplakin, all remain unchanged during EPEC infection in vitro. This evidence is corroborated by the unaltered localization of desmoglein and desmoplakin in vivo in mice infected with C. rodentium for 7 days. Electron microscopic analysis of 7-day C. rodentium-infected murine colonocytes also show no observable differences in the desmosomes when compared to uninfected controls. Our data suggest that, unlike tight junctions, the desmosome protein levels and localization, as well as desmosome morphology, are unaltered during A/E pathogenesis.