Protective mechanism of ferulic acid against neomycin-induced ototoxicity in zebrafish.

Ototoxicity refers to damage of sensory hair cells and functional hearing impairment following aminoglycosides exposure. Previously, we have determined that ferulic acid (FA) protected hair cells against serial concentrations of neomycin-induced ototoxic damage. The aim of the present study is to assess the mechanism and effects of FA on neomycin-induced hair cells loss and impact on mechanosensory-mediated behaviors alteration using transgenic zebrafish (pvalb3b: TagGFP). We first identified the optimal protective condition as pre/co-treatment method in early fish development. Pretreatment of the larvae with FA significantly protected against neomycin-induced hair cells loss through preventing neomycin passed through the cytoplasm of hair cells, and subsequently decreased reactive oxygen species production and TUNEL signals in 4 day post-fertilization (dpf) transgenic zebrafish larvae. Moreover, preservation of functional hair cells correlated directly with rescue of the altered swimming behavior, indicates FA pretreatment protects against neomycin ototoxic damage in 7-dpf transgenic zebrafish larvae. Together, our findings unravel the otoprotective role of FA as an effective agent against neomycin-induced ototoxic effects and offering the theoretical foundation for discovering novel candidates for hearing protection.

Cichoric Acid May Play a Role in Protecting Hair Cells from Ototoxic Drugs.

Ototoxic hearing loss due to antibiotic medication including aminoglycosides and excess free radical production causes irreversible hair cell injury. Cichoric acid, a naturally occurring phenolic acid, has recently been found to exert anti-oxidative and anti-inflammatory properties through its free radical scavenging capacity. The present study aimed to investigate the protective effects of cichoric acid against neomycin-induced ototoxicity using transgenic zebrafish (pvalb3b: TagGFP). Our results indicated that cichoric acid in concentrations up to 5 µM did not affect zebrafish viability during the 2 h treatment period. Therefore, the otoprotective concentration of cichoric acid was identified as 5 µM under 2 h treatment by counting viable hair cells within the neuromasts of the anterior- and posterior-lateral lines in the study. Pretreatment of transgenic zebrafish with 5 µM of cichoric acid for 2 h significantly protected against neomycin-induced hair cell death. Protection mediated by cichoric acid was, however, lost over time. A terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and FM4-64 staining, respectively, provided in situ evidence that cichoric acid ameliorated apoptotic signals and mechanotransduction machinery impairment caused by neomycin. A fish locomotor test (distance move, velocity, and rotation frequency) assessing behavioral alteration after ototoxic damage revealed rescue due to cichoric acid pretreatment before neomycin exposure. These findings suggest that cichoric acid in 5 µM under 2 h treatment has antioxidant effects and can attenuate neomycin-induced hair cell death in neuromasts. Although cichoric acid offered otoprotection, there is only a small difference between pharmacological and toxic concentrations, and hence cichoric acid can be considered a rather prototypical compound for the development of safer otoprotective compounds.

Briarenolides U-Y, New Anti-Inflammatory Briarane Diterpenoids from an Octocoral Briareum sp. (Briareidae).

Five new 13,14-epoxybriarane diterpenoids, briarenolides U-Y (1-5), were isolated from the octocoral Briareum sp. The structures of briaranes 1-5 were elucidated by spectroscopic methods. Briarenolides U-Y (1-5) were found to significantly inhibit the expression of the pro-inflammatory inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein of the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells.

13-acetoxysarcocrassolide induces apoptosis on human gastric carcinoma cells through mitochondria-related apoptotic pathways: p38/JNK activation and PI3K/AKT suppression.

13-acetoxysarcocrassolide (13-AC), an active compound isolated from cultured Formosa soft coral Sarcophyton crassocaule, was found to possess anti-proliferative and apoptosis-inducing activities against AGS (human gastric adenocarcinoma cells) gastric carcinoma cells. The anti-tumor effects of 13-AC were determined by MTT assay, colony formation assessment, cell wound-healing assay, TUNEL/4,6-Diamidino-2-phenylindole (DAPI) staining, Annexin V-fluorescein isothiocyanate/propidium iodide (PI) staining and flow cytometry. 13-AC inhibited the growth and migration of gastric carcinoma cells in a dose-dependent manner and induced both early and late apoptosis as assessed by flow cytometer analysis. 13-AC-induced apoptosis was confirmed through observation of a change in ΔΨm, up-regulated expression levels of Bax and Bad proteins, down-regulated expression levels of Bcl-2, Bcl-xl and Mcl-1 proteins, and the activation of caspase-3, caspase-9, p38 and JNK. Furthermore, inhibition of p38 and JNK activity by pretreatment with SB03580 (a p38-specific inhibitor) and SP600125 (a JNK-specific inhibitor) led to rescue of the cell cytotoxicity of 13-AC-treated AGS cells, indicating that the p38 and the JNK pathways are also involved in the 13-AC-induced cell apoptosis. Together, these results suggest that 13-AC induces cell apoptosis against gastric cancer cells through triggering of the mitochondrial-dependent apoptotic pathway as well as activation of the p38 and JNK pathways.

Oxygenated Cembranoids from the Soft Coral Sinularia flexibilis.

Chemical examination of the Taiwanese soft coral Sinularia flexibilis led to the isolation of five cembrane-based diterpenoids 1-5, including two new metabolites, 11-acetylsinuflexolide (1) and 11-acetyldihydrosinuflexolide (2). The structures of the new metabolites were determined based on extensive spectroscopic analysis, particularly mass spectrometry and 2D NMR (1H-1H COSY, HMQC, HMBC, and NOESY) spectroscopy. Metabolites 1, 3 and 4 exhibited moderate to weak cytotoxicity to human tumor cell lines, HeLa, HEp-2, MCF-7 and MDA-MB-231.

Inhibition of melanogenesis by gallic acid: possible involvement of the PI3K/Akt, MEK/ERK and Wnt/ß-catenin signaling pathways in B16F10 cells.

Gallic acid is one of the major flavonoids found in plants. It acts as an antioxidant, and seems to have anti-inflammatory, anti-viral, and anti-cancer properties. In this study, we investigated the effects of gallic acid on melanogenesis, including the activation of melanogenesis signaling pathways. Gallic acid significantly inhibited both melanin synthesis and tyrosinase activity in a dose- and time-dependent manner, and decreased the expression of melanogenesis-related proteins, such as microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP1), and dopachrome tautomerase (Dct). In addition, gallic acid also acts by phosphorylating and activating melanogenesis inhibitory proteins such as Akt and mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK). Using inhibitors against PI3K/Akt (LY294002) or MEK/ERK-specific (PD98059), the hypopigmentation effect was suppressed, and the gallic acid-initiated activation of MEK/ERK and PI3K/Akt was also revoked. Gallic acid also increased GSK3ß and p-ß-catenin expression but down-regulated p-GSK3ß. Moreover, GSK3ß-specific inhibitor (SB216763) restored gallic acid-induced melanin reduction. These results suggest that activation of the MEK/ERK, PI3K/Akt, and inhibition of Wnt/ß-catenin signaling pathways is involved in the melanogenesis signaling cascade, and that activation by gallic acid reduces melanin synthesis via down-regulation of MITF and its downstream signaling pathway. In conclusion, gallic acid may be a potentially agent for the treatment of certain skin conditions.

Protective Effect of Alpha-Linolenic Acid on Human Oral Squamous Cell Carcinoma Metastasis and Apoptotic Cell Death.

Oral cancer ranks sixth among Taiwan's top 10 cancers and most patients with poor prognosis acquire metastases. The essential fatty acid alpha-linolenic acid (ALA) has been found to diminish many cancer properties. However, the anti-cancer activity of ALA in oral cancer has yet to be determined. We examined the mechanisms underlying ALA inhibition of metastasis and induction of apoptotic cell death in oral squamous cell carcinoma (OSCC). Migration and invasion assays confirmed the cancer cells' EMT capabilities, whereas flow cytometry and Western blotting identified molecular pathways in OSCC. ALA dramatically reduced cell growth in a concentration-dependent manner according to the findings. Low concentrations of ALA (100 or 200 µM) inhibit colony formation, the expression of Twist and EMT-related proteins, the expression of MMP2/-9 proteins, and enzyme activity, as well as cell migration and invasion. Treatment with high concentrations of ALA (200 or 400 µM) greatly increases JNK phosphorylation and c-jun nuclear accumulation and then upregulates the FasL/caspase8/caspase3 and Bid/cytochrome c/caspase9/caspase3 pathways, leading to cell death. Low concentrations of ALA inhibit SAS and GNM cell migration and invasion by suppressing Twist and downregulating EMT-related proteins or by decreasing the protein expression and enzyme activity of MMP-2/-9, whereas high concentrations of ALA promote apoptosis by activating the JNK/FasL/caspase 8/caspase 3-extrinsic pathway and the Bid/cytochrome c/caspase 9 pathway. ALA demonstrates potential as a treatment for OSCC patients.

The Effects of the KCNQ Openers Retigabine and Flupirtine on Myotonia in Mammalian Skeletal Muscle Induced by a Chloride Channel Blocker.

The purpose of this study was to investigate the effect of KCNQ (potassium channel, voltage-gated, KQT-like subfamily) openers in preventing myotonia caused by anthracene-9-carboxylic acid (9-AC, a chloride channel blocker). An animal model of myotonia can be elicited in murine skeletal muscle by 9-AC treatment. KCNQ openers, such as retigabine and flupirtine, can inhibit the increased twitch amplitude (0.1 Hz stimulation) and reduce the tetanic fade (20 Hz stimulations) observed in the presence of 9-AC. Furthermore, the prolonged twitch duration of skeletal muscle was also inhibited by retigabine or flupirtine. Lamotrigine (an anticonvulsant drug) has a lesser effect on the muscle twitch amplitude, tetanic fade, and prolonged twitch duration as compared with KCNQ openers. In experiments using intracellular recordings, retigabine and flupirtine clearly reduced the firing frequencies of repetitive action potentials induced by 9-AC. These data suggested that KCNQ openers prevent the myotonia induced by 9-AC, at least partly through enhancing potassium conductance in skeletal muscle. Taken together, these results indicate that KCNQ openers are potential alternative therapeutic agents for the treatment of myotonia.

Antimelanogenesis Effect of Methyl Gallate through the Regulation of PI3K/Akt and MEK/ERK in B16F10 Melanoma Cells.

Methyl gallate is a polyphenolic compound found in many plants, and its antioxidant, antitumor, antibacterial, and anti-inflammatory effects have been extensively studied. More recently, antidepressant-like effects of methyl gallate have been demonstrated in some studies. In the present study, we examined the effects of methyl gallate on melanogenesis, including the tyrosinase inhibitory effect, the melanin content, and the molecular signaling pathways involved in this inhibition. The results showed that methyl gallate inhibited tyrosinase activity and significantly downregulated the expressions of melanin synthesis-associated proteins, including microphthalmia-associated transcription factor (MITF), tyrosinase, dopachrome tautomerase (Dct), and tyrosinase-related protein-1 (TRP1). In conclusion, our findings indicated that activation of MEK/ERK and PI3K/Akt promoted by methyl gallate caused downregulation of MITF and triggered its downstream signaling pathway, thereby inhibiting the production of melanin. In summary, methyl gallate showed significant inhibitory activity against melanin formation, implying that it may be a potential ingredient for application in skin-whitening cosmetics.

An investigation into the cytotoxic effects of 13-acetoxysarcocrassolide from the soft coral Sarcophyton crassocaule on bladder cancer cells.

Active compounds from natural products have been widely studied. The anti-tumor effects of 13-acetoxysarcocrassolide isolated from Formosan soft coral Sarcophyton crassocaule on bladder cancer cells were examined in this study. An MTT assay showed that 13-acetoxysarcocrassolide was cytotoxic to bladder female transitional cancer (BFTC) cells. We determined that the BFTC cells underwent cell death through apoptosis by flow cytometry. Due to the highly-migratory nature of the BFTC cells, the ability of 13-acetoxysarcocrassolide to stop their migration was assessed by a wound healing assay. To determine which proteins were affected in the BFTC cells upon treatment, a comparative proteomic analysis was performed. By LC-MS/MS analysis, we identified that 19 proteins were up-regulated and eight were down-regulated. Seven of the proteins were confirmed by western blotting analysis. This study reveals clues to the potential mechanism of the cytotoxic effects of 13-acetoxysarcocrassolide on BFTC cells. Moreover, it suggests that PPT1 and hnRNP F could be new biomarkers for bladder cancer. The results of this study are also helpful for the diagnosis, progression monitoring and therapeutic strategies of transitional cell tumors.

A novel mutation in the connexin 29 gene may contribute to nonsyndromic hearing loss.

Connexins (Cxs) are homologous four-transmembrane domain proteins and constitute the major components of gap junctions. Among a cohort of patients with nonsyndromic hearing loss, we recently identified a novel missense mutation, E269D, in the GJC3 gene encoding connexin 29 (Cx29), as being causally related to hearing loss. The functional alteration of Cx29 caused by the mutant GJC3 gene, however, remains unknown. This study compared the intracellular distribution and assembly of mutant Cx29 (Cx29E269D) with that of the wild-type Cx29 (Cx29WT) in HeLa cells and the effect the mutant protein had on those cells. Cx29TW showed continuous staining along apposed cell membranes in the fluorescent localization assay. In contrast, the p.E269D missense mutation resulted in accumulation of the Cx29 mutant protein in the endoplasmic reticulum (ER) rather than in the cytoplasmic membrane. Co-expression of Cx29WT and Cx29E269D proteins by a bi-directional tet-on expression system demonstrated that the heteromeric connexon accumulated in the cytoplasm, thereby impairing the formation of the gap junction. Based on these findings, we suggest that Cx29E269D has a dominant negative effect on the formation and function of the gap junction. These results provide a novel molecular explanation for the role Cx29 plays in the development of hearing loss.

Polymorphisms of the RET gene in hirschsprung disease, anorectal malformation and intestinal pseudo-obstruction in Taiwan.

BACKGROUND/PURPOSE: Mutations in the receptor tyrosine kinase RET gene are associated with Hirschsprung disease (HD), which is also known as congenital intestinal aganglionosis. We found an association with specific alleles in five single nucleotide polymorphism (SNP) sites of the RET gene in our HD patients. METHODS: We compared the association of specific RET SNP alleles in patients with severe GI disorders such as anorectal malformation (ARM) or pediatric intestinal pseudo-obstruction (IPO) to that in HD patients. Sixty-four HD, 23 ARM and 35 IPO patients were included. Genomic DNA extracted from blood samples was analyzed by polymerase chain reaction and DNA sequencing analysis. RESULTS: The allele distributions of all five RET SNPs in the HD patients deviated from those in the normal population (p < 0.05), whereas those of the ARM patients did not. The allele distributions of these RET SNPs in the IPO patients were all significantly different from those in the HD patients. Allele distributions of exon 2 and 13 in the IPO patients were also significantly different from those of the normal population. The frequencies of all the HD-predominant alleles were lower in the HD patients than the normal population, and were even lower in the IPO patients. CONCLUSION: This study strengthens the association of specific RET SNP alleles with typical HD in Taiwan.

The Functional Role of CONNEXIN 26 Mutation in Nonsyndromic Hearing Loss, Demonstrated by Zebrafish Connexin 30.3 Homologue Model.

Nonsyndromic hearing loss (NSHL) is of great clinical importance, and mutations in the GJB2 gene and the encoded human CONNEXIN 26 (CX26) protein play important roles in the genetic pathogenesis. The CX26 p.R184Q mutation was shown to be a dominant-negative effect in our previous study. Previously, we also demonstrated that zebrafish Cx30.3 is orthologous to human CX26. In the present study, we established transgenic zebrafish models with mutated Cx30.3 specifically expressed in the supporting cells of zebrafish inner ears driven by the agr2 promoter, to demonstrate and understand the mechanism by which the human CX26 R.184 mutation causes NSHL. Our results indicated that significant structural changes in the inner ears of transgenic lines with mutations were measured and compared to wild-type zebrafish. Simultaneously, significant alterations of transgenic lines with mutations in swimming behavior were analyzed with the zebrafish behavioral assay. This is the first study to investigate the functional results of the CX26 p.R184Q mutation with in vivo disease models. Our work supports and confirms the pathogenic role of the CX26 p.R184Q mutation in NSHL, with a hypothesized mechanism of altered interaction among amino acids in the connexins.

Paraneoplastic polymyositis associated with crescentic glomerulonephritis.

A female concurrently developed polymyositis (PM), lung cancer, and nephrotic range proteinuria. Renal biopsy revealed crescentic glomerulonephritis. Pathology of lung cancer was proved to be adenocarcinoma. After surgical treatment of lung cancer, the symptoms of PM-associated crescentic glomerulonephritis disappeared. PM is associated with a higher risk of malignancy, though renal involvement in patients with PM is thought to be uncommon. In patients with PM, there have been few reports concerning the coexistence of glomerular disease, including crescent glomerulonephritis. Herein we report a case of crescentic glomerulonephritis-associated PM that was successfully treated after the surgical removal of lung cancer. We consider that such association of PM and crescent glomerulonephritis is rare in adults. Careful evaluation of underlying malignancy is important. The definite treatment is adequate management of underlying malignancy.

Proteomic analysis of peritoneal dialysate fluid in patients with dialysis-related peritonitis.

The prognosis of uremia patients on continuous ambulatory peritoneal dialysis (CAPD) is related to frequent peritonitis rate. Frequent peritonitis will lead to peritoneum failure, making CAPD unfeasible. We have performed proteomic profiling of peritoneal dialysis effluent samples from a cross-section of CAPD patients with and without peritonitis in order to identify biomarkers of peritonitis. We performed 2D gel electrophoresis and surface-enhanced laser esorption/ionization time of flight mass spectrometry (SELDI-TOF MS) on peritoneal dialysis effluent from 16 subjects with peritonitis. A genetic algorithm search of principal component space revealed a group of a peak distinguishing peritonitis-positive subjects, with mass/charge (m/z) values of 11,117.4. Our analyses identified the peak at m/z 11,117.4 with an accuracy of 95% for classifying peritonitis. Mass spectrometric analysis of peritonitis PDE samples identified the 11,117.4 protein as beta2-microglobulin (B2M). Using an unbiased protein profiling approach, we have validated previously reported findings of B2M as a biomarker associated with CAPD peritonitis. Prospective studies are warranted to establish additional biomarkers that would be predictive of peritoneal dialysis peritonitis. Besides, extending the study to a larger number of patients with subgroup analyses may yield additional information of the peritoneal dialysate proteins in association with dialysis adequacy, residual renal function, nutritional status, and risk of peritoneal infection.

Fas expression on peritoneal macrophages during continuous ambulatory peritoneal dialysis peritonitis.

BACKGROUND: Peritonitis is a common complication of end stage renal failure (ESRF) patients receiving continuous ambulatory peritoneal dialysis (CAPD). Peritoneal macrophage may participate in the activation of specific T cells and in the generation of local cell-mediated immunity to various pathogens. The purpose of this study is to investigate the possible role of macrophage in CAPD patients with peritonitis. METHODS: We evaluated the expression of Fas receptor (CD95), ICAM-1 (CD54), CD25, and CD69 by two-color flow cytometry on extravasted macrophages from 16 ESRF patients on CAPD with peritonitis (peritonitis-positive) and compared them to 11 ESRF patients on CAPD without peritonitis (peritonitis-negative) and normal controls. RESULTS: We found an increased expression of CD95, CD54, and CD25 on macrophage in peritonitis-positive group compared to controls (all p < 0.001). In the peritonitis-positive group, the CD95 expression was significantly higher than that of the peritonitis-negative group (p < 0.001). The expression of CD54, CD25, and CD69, however, was not significantly different between the peritonitis-positive and peritonitis-negative CAPD subgroups. CONCLUSION: We found an abnormally increased percentage of macrophage-expressing Fas receptor and ICAM-1, and the percentage of CD95+ macrophage, but not those of other markers, were increased among the subset of CAPD patients with peritonitis. The later finding suggests that this macrophage phenotype is associated with peritonitis occurring in CAPD.

Induction of oxidative stress response by the mycotoxin patulin in mammalian cells.

Patulin (PAT), a mycotoxin mainly produced by Penicillium and Aspergillus, is found in various foods and feeds. In the present study, its effects on oxidative stress in various mammalian cell lines were investigated. When cell-permeating fluorescent dyes were used as indicators of the generation of reactive oxygen species (ROS), we found that PAT treatment directly increased intracellular oxidative stress in human embryonic kidney (HEK293) and human promyelocytic leukemia (HL-60) cells. Lipid peroxidation levels were also significantly increased in HL-60 cells and mouse kidney homogenates treated with PAT. Suppression of CuZn-superoxide dismutase (SOD) expression in mammalian cells by small interfering RNA resulted in an increase in PAT-mediated membrane damage, while overexpression of human CuZn-SOD or catalase led to a reduction in damage, indicating the involvement of ROS in PAT toxicity. Pretreatment of HEK293 cells with Tiron, a free radical scavenger, reduced the phosphorylation levels of extracellular signal-regulated kinase (ERK) 1/2 elicited by PAT. The ERK1/2 signaling pathway inhibitor, U0126, also significantly decreased the levels of ROS associated with PAT treatment. These findings indicate that PAT treatment results in the ROS production in mammalian cells, and ROS partially contributes to PAT-induced cytotoxicity. Activation of ERK1/2 signaling pathway is correlated with PAT-mediated ROS.

Identification of mutations in members of the connexin gene family as a cause of nonsyndromic deafness in Taiwan.

Connexins (Cx), a large family of membrane proteins, are key components of gap junction channels. These channels are critical intercellular pathways through which ions or small molecules are passed, regulating a variety of physiological and developmental processes. One of these processes is hearing. In the current study, a genetic survey was made on 380 Taiwanese individuals, 260 with nonsyndromic deafness and 120 with normal hearing. All the 380 Taiwanese were screened for the presence of mutations in 8 genes of the Cx gene family. These genes included Cx26 (GJB2), Cx29 (GJE1), Cx30 (GJB6), Cx30.3 (GJB4), Cx31 (GJB3), Cx32 (GJB1), Cx43 (GJA1) and pseudogene [rho] of Cx43 (rho GJA1). Mutations were identified in 7 out of the 8 screened genes of the Cx family from 62 of the 260 deaf subjects (23.85%). Of the 17 mutations observed in the Cx gene family, 11 were novel mutations. Fourteen polymorphisms that were not associated with hearing loss were identified in the Cx gene family. The first 2 most frequently occurring mutations were found in the Cx26 (28/62; 45.16%) and the rho Cx43 (17/62; 27.42%), respectively. Nine cases of mutations were found in the Cx30.3 (9/62; 14.52%). In the Cx30, 1 novel mutation was identified in 1 case (1/62; 1.61%). Two patients with mutations of each of Cx29 and Cx43 were found (2/62; 3.23%). One novel mutation of Cx31 was identified in 3 patients with nonsyndromic deafness (3/62; 4.84%). The Cx32 was the only gene without detecting any mutation or polymorphism.Our study provides information for understanding the importance of genetic factors in nonsyndromic deafness of the Taiwanese and may be of use in the improvement of genetic diagnosis of hearing loss in Taiwan.

Development of a monoclonal antibody against domoic acid and its application in enzyme-linked immunosorbent assay and colloidal gold immunostrip.

A monoclonal antibody (mAb) specific to domoic acid was produced from a stable hybridoma cell line, 9F1F11, generated by the fusion of P3/NS1/1-AG4-1 myeloma cells with spleen cells isolated from a Balb/c mouse immunized with domoic acid--keyhole limpet hemocyanin. The 9F1F11 mAb belongs to the immunoglobulin G1 (kappa-chain) isotype. A competitive direct enzyme-linked immunosorbent assay (cdELISA) and a competitive indirect ELISA were established for antibody characterization. In the cdELISA, the concentration causing 50% inhibition (IC50) of binding of domoic acid-horseradish peroxidase to the antibody by domoic acid was found to be 0.58 ng/mL. A sensitive and rapid mAb-based colloidal gold immunostrip was also developed. The immunostrip assay, which has a detection limit of 5 ng/mL for domoic acid, can be completed in 10 min. Analysis of domoic acid in blue mussel samples revealed that data obtained from immunostrip were in a good agreement with those obtained from cdELISA. The mAb-based cdELISA and immunostrip assay established in this study were sensitive and accurate for rapid screening of domoic acid in shellfish samples.

Elevated transglutaminase-2 expression in the epidermis of psoriatic skin and its role in the skin lesion development.

Psoriasis, an inflammatory skin disease triggered by the immune system, presents keratinocyte hyperproliferation, differentiation and angiogenesis. The role of transglutaminase-2 (TG2) in psoriasis has not been fully established yet. In this retrospective, non-randomized and non-blinded study, skin biopsies were collected from 37 psoriatic patients and immunohistochemical staining was performed. TG2 staining was positive in all 37 samples, among which 32 were strong and five weak. The localization of TG2 staining was present in the epidermis and spreading from basal layer to stratum granulosum in decreasing staining intensity. However, TG2 was also expressed in the basal layer in the non-lesional site of psoriasis and the skin of healthy people. The presence of TG2 was not associated with disease duration, stage of disease and subtype of psoriasis. Overexpression of TG2 seems to be an important role in psoriatic development.