scholarly journals Expression of the JAK/STAT Signaling Pathway in Bullous Pemphigoid and Dermatitis Herpetiformis

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
K. Juczynska ◽  
A. Wozniacka ◽  
E. Waszczykowska ◽  
M. Danilewicz ◽  
M. Wagrowska-Danilewicz ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Bullous Pemphigoid ◽  
Target Genes ◽  
Dermatitis Herpetiformis ◽  
Skin Lesions ◽  
Control Group ◽  
Cytokine Network ◽  
Activation Of Transcription ◽  
Autoimmune Bullous Diseases ◽  
Stat Signaling

A family of eleven proteins comprises the Janus kinases (JAK) and signal transducers and activators of transcription (STAT) signaling pathway, which enables transduction of signal from cytokine receptor to the nucleus and activation of transcription of target genes. Irregular functioning of the cascade may contribute to pathogenesis of autoimmune diseases; however, there are no reports concerning autoimmune bullous diseases yet to be published. The aim of this study was to evaluate the expression of proteins constituting the JAK/STAT signaling pathway in skin lesions and perilesional area in dermatitis herpetiformis (DH) and bullous pemphigoid (BP), as well as in the control group. Skin biopsies were collected from 21 DH patients, from 20 BP patients, and from 10 healthy volunteers. The localization and expression of selected STAT and JAK proteins were examined by immunohistochemistry and immunoblotting. We found significantly higher expression of JAK/STAT proteins in skin lesions in patients with BP and DH, in comparison to perilesional skin and the control group, which may be related to proinflammatory cytokine network and induction of inflammatory infiltrate in tissues. Our findings suggest that differences in the JAK and STAT expression may be related to distinct cytokines activating them and mediating neutrophilic and/or eosinophilic infiltrate.

scholarly journals The Role of Intereukin-31 in Pathogenesis of Itch and Its Intensity in a Course of Bullous Pemphigoid and Dermatitis Herpetiformis

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Lilianna Kulczycka-Siennicka ◽  
Anna Cynkier ◽  
Elżbieta Waszczykowska ◽  
Anna Woźniacka ◽  
Agnieszka Żebrowska
Keyword(s):  
Signaling Pathway ◽  
Bullous Pemphigoid ◽  
Dermatitis Herpetiformis ◽  
Subjective Symptoms ◽  
Autoimmune Blistering Disease ◽  
Stat Signaling ◽  
Blistering Disease ◽  
Autoimmune Blistering Diseases

Itch which is one of the major, subjective symptoms in a course of bullous pemphigoid and dermatitis herpetiformis makes those two diseases totally different than other autoimmune blistering diseases. Its pathogenesis is still not fully known. The aim of this research was to assess the role of IL-31 in development of itch as well as to measure its intensity. Obtained results, as well as literature data, show that lower concentration of IL-31 in patients’ serum may be correlated with its role in JAK/STAT signaling pathway which is involved in development of autoimmune blistering disease. Intensity of itch is surprisingly huge problem for the patients and the obtained results are comparable with results presented by atopic patients.

scholarly journals Long non-coding RNA RP11-468E2.5 curtails colorectal cancer cell proliferation and stimulates apoptosis via the JAK/STAT signaling pathway by targeting STAT5 and STAT6

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Li Jiang ◽  
Xu-Hai Zhao ◽  
Yin-Ling Mao ◽  
Jun-Feng Wang ◽  
Hui-Jun Zheng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Target Genes ◽  
Biological Activities ◽  
Janus Kinase ◽  
Normal Tissues ◽  
Stat Signaling

Abstract Background Long non-coding RNAs (lncRNAs) are tumor-associated biological molecules and have been found to be implicated in the progression of colorectal cancer (CRC). This study aims to examine the effects of lncRNA RP11-468E2.5 and its target genes (STAT5 and STAT6) on the biological activities of CRC cells via the Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway. Methods We initially screened the GEO database for differentially expressed lncRNAs related to CRC and then made a prediction of the implicated target genes. Then we collected CRC tissues and adjacent normal tissues from 169 CRC patients. Human CRC HCT116 and SW480 cells were treated with small interference RNA (siRNA) against RP11-468E2.5, AG490 (an inhibitor of the JAK/STAT signaling pathway), or both in combination. Next, we measured the effects of RP11-468E2.5 treatment on cellular activities such as cell viability, cycle distribution and cell apoptosis, and studied interactions among RP11-468E2.5, STAT5/STAT6, and the JAK/STAT signaling pathway. Finally, an in vivo tumor formation assay was performed to observe the effect of RP11-468E2.5 on tumor growth. Results The CRC-related gene microarray data showed low expression of RP11-468E2.5 in CRC surgical specimens. However, RP11-468E2.5 was confirmed to target STAT5 and STAT6, which participate in the JAK/STAT signaling pathway. CRC tissues showed lower expression of RP11-468E2.5, higher expression of STAT5, STAT6 and of the cell cycle marker Cyclin D1 (CCND1), compared to the findings in adjacent normal tissues. The treatment of siRNA against RP11-468E2.5 increased expression of JAK2, STAT3, STAT5, STAT6, CCND1 and Bcl-2 along with the extent of STAT3, STAT5 and STAT6 phosphorylation, while lowering expression of P21 and P27. Treatment with AG490 exhibited approximately opposite effects, whereas siRNA against RP11-468E2.5 treatment stimulated CRC cell proliferation and reduced cell apoptosis, while promoting cell cycle entry; AG490 treatment reversed these results. Conclusions Altogether, we conclude that up-regulation of RP11-468E2.5 inhibits the JAK/STAT signaling pathway by targeting STAT5 and STAT6, thereby suppressing cell proliferation and promoting cell apoptosis in CRC.

The effect of manganese exposure on GnRH secretion via Nrf2/mGluR5/COX-2/PGE2/signaling pathway

2019 ◽  
Vol 35 (3) ◽  
pp. 211-227 ◽  
Author(s):  
Zhipeng Qi ◽  
Chao Mi ◽  
Fengdi Wu ◽  
Xinxin Yang ◽  
Yanqi Sang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Metabotropic Glutamate Receptor ◽  
Morphological Changes ◽  
Control Group ◽  
Related Factor ◽  
Gnrh Secretion ◽  
Cox 2

There are limited studies focused on the precise mechanism of gonadotropin-releasing hormone (GnRH) secretion dysfunction after overexposure to manganese (Mn). The objective of the present study was to explore the mechanism of Mn disruption of GnRH synthesis via nuclear factor erythroid-2-related factor-2 (Nrf2)/metabotropic glutamate receptor-5 (mGluR5)/cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) signaling pathway in vitro and in vivo. Primary astrocytes were cultured and treated with different doses of Mn, tert-butylhydroquinonet (tBHQ; Nrf2 agonists), 3-[(2-methyl-4-thaizolyl) ethynyl] pyridine (MTEP; mGluR5 inhibitor), and celecoxib (COX-2 inhibitor) to measure the levels of COX-2, mGluR5, Nrf2, and Nrf2 target genes. Mice were randomly divided into 11 groups, of which included the control group, 12.5-, 25-, and 50-mg/kg MnCl2 group, dimethyl sulfoxide (DMSO) group, tBHQ control group, tBHQ pretreatment group, MTEP control group, MTEP pretreatment group, celecoxib control group, and celecoxib pretreatment group. The injection was administered every day for 2 weeks. Then, levels of GnRH, PGE2, COX-2, mGluR5, Nrf2, Nrf2 target genes, and morphological changes in the hypothalamus of mice were measured. Mn reduced protein levels of Nrf2 and mRNA expression of Nrf2 target genes and increased mGluR5, COX-2, PGE2, and GnRH levels. Meanwhile, injury-related histomorphology changes in the hypothalamus of mice were significantly present. In conclusion, excessive exposure to Mn disrupts GnRH secretion through Nrf2/mGluR5/COX-2/PGE2 signaling pathway.

scholarly journals Mediators of Mast Cells in Bullous Pemphigoid and Dermatitis Herpetiformis

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Agnieszka Zebrowska ◽  
Malgorzata Wagrowska-Danilewicz ◽  
Marian Danilewicz ◽  
Olga Stasikowska-Kanicka ◽  
Lilianna Kulczycka-Siennicka ◽  
...  
Keyword(s):  
Mast Cells ◽  
Bullous Pemphigoid ◽  
Skin Diseases ◽  
Dermatitis Herpetiformis ◽  
Skin Lesions ◽  
Autoimmune Blistering Disease ◽  
Mmp9 Expression ◽  
Skin Biopsies ◽  
Cell Expression ◽  
Perilesional Skin

Bullous pemphigoid (BP) and dermatitis herpetiformis (DH) are skin diseases associated with inflammation. However, few findings exist concerning the role of mast cells in autoimmune blistering disease. Skin biopsies were taken from 27 BP and 14 DH patients, as well as 20 healthy individuals. Immunohistochemistry was used to identify the localization and mast cell expression of TNFα and MMP9 in skin lesions and perilesional skin. The serum concentrations of TNFα, MMP9, chymase, tryptase, PAF, and IL-4 were measured by immunoassay. TNFα and MMP9 expression in the epidermis and in inflammatory influxed cells in the dermis was detected in skin biopsies from patients. Although these mediators were found to be expressed in the perilesional skin of all patients, the level was much lower than that in lesional skin. Increased serum PAF levels were observed in BP patients. Mast cells may play an essential role in activating inflammation, which ultimately contributes to the tissue damage observed in BP and DH. Our findings suggest that differences in the pattern of cytokine expression directly contribute to variations in cellular infiltration in DH and BP.

scholarly journals Expression of MMP-2 and MMP-13 in Bullous Pemphigoid

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Haixiang Zhang ◽  
Xiaoxu Shi ◽  
Lanying Qin ◽  
Zishen Zhao ◽  
Guojun Fu ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Bullous Pemphigoid ◽  
Normal Control ◽  
Normal Skin ◽  
Skin Lesions ◽  
Normal Control Group ◽  
High Expression ◽  
Matrix Metalloproteinase 2 ◽  
Control Group ◽  
Case Group

Objective: To investigate the expression and significance of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-13 (MMP-13) in bullous pemphigoid (BP) skin lesions. Methods: Immunohistochemical SP method was used to detect the expression of MMP-2 and MMP-13 in 32 BP skin lesions, and compared with 15 normal skin tissues. Results: The expression of MMP-2 in the case group was significantly increased (38.56 ± 10.06) compared to the normal control group (21.20 ± 5.98); the expression of MMP-13 in the case group was significantly augmented (18.62 ± 5.90) compared to the normal control group (11.47 ± 8.484). The expressions of MMP-2 and MMP-13 in the skin lesions of patients with bullous pemphigoid were statistically different from those of normal people (both P < 0.05). Compared with the expression of MMP-2 and MMP-13 in bullous pemphigoid, the expression of MMP-2 and MMP-13 was moderately correlated (correlation coefficient was 0.523). Conclusion: The expression of MMP-2 and MMP-13 is significantly increased in bullous pemphigoid skin lesions, suggesting that they may play an important role in the pathogenesis of BP. There is a certain correlation between the expression of MMP-2 and MMP-13, suggesting that the high expression of MMP-13 may play a role in the mechanism that further leads to the high expression of MMP-2.

scholarly journals Expression of Selected Integrins and Selectins in Bullous Pemphigoid

2007 ◽  
Vol 2007 ◽  
pp. 1-7 ◽  
Author(s):  
Agnieszka Żebrowska ◽  
Anna Sysa-Jędrzejowska ◽  
Małgorzata Wągrowska-Danilewicz ◽  
Ewa Joss-Wichman ◽  
Anna Erkiert-Polguj ◽  
...  
Keyword(s):  
Bullous Pemphigoid ◽  
Healthy Subjects ◽  
Skin Lesions ◽  
Control Group ◽  
Dermoepidermal Junction ◽  
Basal Keratinocytes ◽  
Membrane Components ◽  
Inflammatory Infiltrates ◽  
Basement Membrane Components

Blister development in bullous pemphigoid (BP) results from destruction of hemidesmosomes and basement membrane components within the dermoepidermal junction by autoantibodies. Adhesion molecules can take part in pathogenesis of this disease. The aim of the study was to determine the localization and expression of L- and E-selectins andβ1,β3, andβ4 integrins by immunohistochemistry in skin lesions of 21 patients with BP, compared with 10 healthy subjects. Expression of L and E selectins andβ1,β3 integrins was detected mainly in basal keratinocytes and in inflammatory infiltrates in the dermis, expression ofβ4 integrin was irregular and was detected mainly in dermal part of the blister, while in the control group only weak and single expression of the examined molecules was detected in basal keratinocytes and endothelium cells. The obtained results reveal the important role of selected selectins and integrins in development of skin lesions in BP.

scholarly journals N6-Methyladenosine Methylation Analysis of Long Noncoding RNAs and mRNAs in IPEC-J2 Cells Treated With Clostridium perfringens beta2 Toxin

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiaojiao Yang ◽  
Qiaoli Yang ◽  
Juanli Zhang ◽  
Xiaoli Gao ◽  
Ruirui Luo ◽  
...  
Keyword(s):  
Immune Response ◽  
Signaling Pathway ◽  
Clostridium Perfringens ◽  
Defense Response ◽  
Target Genes ◽  
Wnt Signaling Pathway ◽  
Control Group ◽  
Infectious Diarrhea ◽  
Type C

BackgroundThe n6-methyladenosine (m6A) modification is present widely in mRNAs and long non-coding RNAs (lncRNAs), and is related to the occurrence and development of certain diseases. However, the role of m6A methylation in Clostridium perfringens type C infectious diarrhea remains unclear.MethodsHere, we treated intestinal porcine jejunum epithelial cells (IPEC-J2 cells) with Clostridium perfringens beta2 (CPB2) toxin to construct an in vitro model of Clostridium perfringens type C (C. perfringens type C) infectious diarrhea, and then used methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) to identify the methylation profiles of mRNAs and lncRNAs in IPEC-J2 cells.ResultsWe identified 6,413 peaks, representing 5,825 m6A-modified mRNAs and 433 modified lncRNAs, of which 4,356 m6A modified mRNAs and 221 m6A modified lncRNAs were significantly differential expressed between the control group and CPB2 group. The motif GGACU was enriched significantly in both the control group and the CPB2 group. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analysis showed that the differentially methylated modified mRNAs were mainly enriched in Hippo signaling pathway and Wnt signaling pathway. In addition, the target genes of the differentially m6A modified lncRNAs were related to defense response to virus and immune response. For example, ENSSSCG00000042575, ENSSSCG00000048701 and ENSSSCG00000048785 might regulate the defense response to virus, immune and inflammatory response to resist the harmful effects of viruses on cells.ConclusionIn summary, this study established the m6A transcription profile of mRNAs and lncRNAs in IPEC-J2 cells treated by CPB2 toxin. Further analysis showed that m6A-modified RNAs were related to defense against viruses and immune response after CPB2 toxin treatment of the cells. Threem6A-modified lncRNAs, ENSSSCG00000042575, ENSSSCG00000048785 and ENSSSCG00000048701, were most likely to play a key role in CPB2 toxin-treated IPEC-J2 cells. The results provide a theoretical basis for further research on the role of m6A modification in piglet diarrhea.

scholarly journals Aberrant Expressional Profiling of Known MicroRNAs in the Liver of Silver Carp (Hypophthalmichthys molitrix) Following Microcystin-LR Exposure Based on samllRNA Sequencing

Toxins ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 41 ◽  
Author(s):  
Yiyi Feng ◽  
Xi Chen ◽  
Junguo Ma ◽  
Bangjun Zhang ◽  
Xiaoyu Li
Keyword(s):  
Signaling Pathway ◽  
High Throughput Sequencing ◽  
Target Genes ◽  
Liver Toxicity ◽  
Silver Carp ◽  
Wnt Signaling Pathway ◽  
Enrichment Analysis ◽  
Control Group ◽  
Hypophthalmichthys Molitrix ◽  
Multiple Organs

Microcystin-LR (MC-LR) poses a serious threat to human health due to its hepatotoxicity. However, the specific molecular mechanism of miRNAs in MC-LR-induced liver injury has not been determined. The aim of the present study was to determine whether miRNAs are regulated in MC-LR-induced liver toxicity by using high-throughput sequencing. Our research demonstrated that 53 miRNAs and 319 miRNAs were significantly changed after 24 h of treatment with MC-LR (50 and 200 μg/kg, respectively) compared with the control group. GO enrichment analysis revealed that these target genes were related to cellular, metabolic, and single-organism processes. Furthermore, KEGG pathway analysis demonstrated that the target genes of differentially expressed miRNAs in fish liver were primarily involved in the insulin signaling pathway, PPAR signaling pathway, Wnt signaling pathway, and transcriptional misregulation in cancer. Moreover, we hypothesized that 4 miRNAs (miR-16, miR-181a-3p, miR-451, and miR-223) might also participate in MC-LR-induced toxicity in multiple organs of the fish and play regulatory roles according to the qPCR analysis results. Taken together, our results may help to elucidate the biological function of miRNAs in MC-LR-induced toxicity.

scholarly journals The Landscape of Non-Coding RNA in an Adult Pig Model of Intrauterine Growth Restriction

2018 ◽  
Vol 50 (5) ◽  
pp. 1764-1778 ◽  
Author(s):  
Linyuan Shen ◽  
Shunhua Zhang ◽  
Qiang Li ◽  
Yuhua Fu ◽  
Guoqing Tang ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Signaling Pathway ◽  
Intrauterine Growth Restriction ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Growth Restriction ◽  
Differentially Expressed ◽  
Quality Data ◽  
Control Group ◽  
Intrauterine Growth

Background/Aims: Intrauterine growth restriction (IUGR) is a risk factor for adult metabolic syndrome, but how this disease is regulated by lncRNAs and circRNAs remains elusive. Methods: Here, we employed adult IUGR and normal pigs as models to evaluate the expression of various global lncRNAs and circRNAs in pig livers using RNA-seq. Results: In total, we obtained 1,162 million raw reads of approximately 104.54 Gb high quality data. After a strict five-step filtering process, 3,368 lncRNAs were identified, including 300 differentially expressed lncRNAs (p < 0.05) in the IUGR group relative to the control group. The cis-regulatory analysis identified target genes that were enriched in specific GO terms and pathways (p < 0.05), including amino acid metabolism, oxidoreductase activity, PPAR signaling pathway, and insulin signaling pathway. These are closely related to the observed phenotypes of increased gluconeogenesis and impaired mitochondrial oxidative phosphorylation in adulthood of the IUGR group. Additionally, we also identified 403 circRNAs, of which 44 were differentially expressed (p < 0.05). Interestingly, our results identified ATF4-miR214-circRNA7964 and TCF7-miR22-3p-circRNA16347 as two competing endogenous networks, which were closely associated with the observed increase in hepatic gluconeogenesis in the IUGR group. Conclusion: Together, this study reveals a multitude of candidate lncRNAs and circRNAs involved in the development of IUGR pigs, which could facilitate further researches on the molecular mechanisms of metabolic syndrome.

scholarly journals IL-17 Expression in Dermatitis Herpetiformis and Bullous Pemphigoid

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Agnieszka Zebrowska ◽  
Malgorzata Wagrowska-Danilewicz ◽  
Marian Danilewicz ◽  
Olga Stasikowska-Kanicka ◽  
Anna Cynkier ◽  
...  
Keyword(s):  
Bullous Pemphigoid ◽  
Healthy Subjects ◽  
Inflammatory Process ◽  
Essential Role ◽  
Skin Diseases ◽  
Dermatitis Herpetiformis ◽  
Control Group ◽  
Bullous Diseases ◽  
Skin Biopsies ◽  
Perilesional Skin

Dermatitis herpetiformis (DH) and bullous pemphigoid (BP) are skin diseases associated with eosinophilic and neutrophilic infiltrations. Although cytokines are critical for the inflammatory process, there are single findings concerning concentration of IL-17 in bullous diseases. The goal of this study was to assess IL-17 expression in DH and BP patients. Skin biopsies were taken from 10 DH, 14 BP patients and from 10 healthy subjects. The localization and expression of IL-17 was studied by immunohistochemistry and the serum concentration was measured by immunoassays. Expression of IL-17 in the epidermis and in influxed cells in dermis was detected in skin biopsies. Expression of IL-17 was statistically higher in epidermis and infiltration cells in specimens from BP than from DH patients. Examined interleukin expression was detected in perilesional skin of all patients but it was much lower than in lesional skin. The expression of IL-17 was not observed in biopsies from healthy people. Serum level of IL-17 was statistically higher in BP and DH groups as compared to control group. Our results provide the evidence that IL-17 may play an essential role in activating and recruiting eosinophils and neutrophils, which ultimately contribute to the tissue damage in DH and BP.

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