scholarly journals Differential Expression of MicroRNAs and their Possible Roles in Patients with Chronic Idiopathic Urticaria and Active Hives

2017 ◽  
Vol 8 (2) ◽  
pp. ar.2017.8.0199 ◽  
Author(s):  
Ching-Kow E. Lin ◽  
John S. Kaptein ◽  
Javed Sheikh
Keyword(s):  
Signaling Pathway ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Chronic Idiopathic Urticaria ◽  
Receptor Interaction ◽  
Messenger Rnas ◽  
P53 Signaling ◽  
Autoimmune Urticaria ◽  
Complicated Skin ◽  
P21 Activated Kinase

Background Chronic idiopathic urticaria (CIU) is a complicated skin disease with unknown pathophysiology. MicroRNAs (miRNA) have been shown to be active in cellular regulation. The goal of this pilot study was to examine whether miRNAs may be involved in the regulation of CIU or as biomarkers for CIU. Methods Four groups of three patients each were selected: patients with either active hives or no hives and with positive or negative chronic urticaria (CU) index results. MiRNAs were isolated from patient plasma and analyzed by using miRNA microarray technology to determine the amount of each of the 2567 known human miRNAs. Results A total of 16 miRNAs were found to be differentially expressed in patients with active hives. Among them, five (2355–3p, 4264, 2355–5p, 29c-5p, and 361–3p) were significantly increased in samples with positive CU index results, which could be useful biomarkers for patients with chronic autoimmune urticaria. The miRNA data bases were used to find the targets of these selected miRNA sequences. These potential targets were then compared against a list of 154 urticaria-related genes. Twenty-five genes were found to match. These included eight that were significantly downregulated and eight that were significantly upregulated; however, seven of the eight downregulated genes (FBXL20, OPHN1, YPEL2, STARD9, EZH1, KLHL24, ING4) and five of the eight upregulated genes (BYSL, PNO1, ADAMTS9, STEAP4, SRGN) have no reported roles in signaling. For the 13 genes with reported roles in signaling, the following pathways were found: transforming growth factor beta signaling pathway (NRC31, KITLG, THBS1, CCL2), glucocorticoid receptor signaling pathway (NR3C1, SELE, CCL2), p53 signaling pathway (CCNG2, THBS1, CCL2), p21-activated kinase pathway (PAK1IP1, KITLG, CCL2), phosphoinositide-3 kinase protein kinase B signaling pathway (KITLG, CHRM, THBS1), and neuroactive ligand-receptor interaction (NRC31, HRH1, CHRM), which could play important roles in CIU. Conclusion A better understanding of those genes with undefined function and simultaneous quantitation of both miRNAs and messenger RNAs are needed to fully understand CIU disease.

scholarly journals Targeting TGF-β-Mediated SMAD Signaling Pathway via Novel Recombinant Cytotoxin II: A Potent Protein from Naja naja oxiana Venom in Melanoma

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5148
Author(s):  
Afshin Derakhshani ◽  
Nicola Silvestris ◽  
Nima Hemmat ◽  
Zahra Asadzadeh ◽  
Mahdi Abdoli Shadbad ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Inhibitory Effect ◽  
Melanoma Cells ◽  
Smad Signaling ◽  
Diphenyltetrazolium Bromide ◽  
Smad Signaling Pathway ◽  
Matrix Metallopeptidase ◽  
Tumoral Cells

Since the current treatments have not resulted in the desired outcomes for melanoma patients, there is a need to identify more effective medications. Together with other snake venom proteins, cytotoxin-II has shown promising results in tumoral cells. In this study, recombinant cytotoxin-II (rCTII) was expressed in SHuffle® T7 Express cells, while the epitope mapping of rCTII was performed to reveal the antibody-binding regions of rCTII. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to assess the viability of SK-MEL-3 and HFF-2 cells after treating these cells with rCTII. The qRT-PCR was performed to evaluate the expression levels of matrix metallopeptidase 3 (MMP-3), SMAD2, SMAD3, caspase-8, caspase-9, and miR-214 in order to reveal the rCTII-induced signaling pathways in melanoma. Our results have shown that two regions of amino acids, 6–16 and 19–44, as predicted epitopes of this toxin, are essential for understanding the toxicity of rCTII. Treating the melanoma cells with rCTII substantially inhibited the transforming growth factor-beta (TGF-β)–SMAD signaling pathway and down-regulated the expression of MMP-3 and miR-214 as well. This cytotoxin also restored apoptosis mainly via the intrinsic pathway. The down-regulation of MMP-3 and miR-214 might be associated with the anti-metastatic property of rCTII in melanoma. The inhibitory effect of rCTII on the TGF-β signaling pathway might be associated with increased apoptosis and decreased cancer cell proliferation. It is interesting to see that the IC50 value of rCTII has been lower in the melanoma cells than non-tumoral cells, which may indicate its potential effects as a drug. In conclusion, rCTII, as a novel medication, might serve as a potent and efficient anticancer drug in melanoma.

scholarly journals Transforming Growth Factor-Beta (TGFβ) Signaling Pathway in Cholangiocarcinoma

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 960 ◽  
Author(s):  
Panagiotis Papoutsoglou ◽  
Corentin Louis ◽  
Cédric Coulouarn
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Tgfβ Signaling ◽  
Efficient Treatment ◽  
Tumor Onset ◽  
Tgfβ Signaling Pathway

Cholangiocarcinoma is a deadly cancer worldwide, associated with a poor prognosis and limited therapeutic options. Although cholangiocarcinoma accounts for less than 15% of liver primary cancer, its silent nature restricts early diagnosis and prevents efficient treatment. Therefore, it is of clinical relevance to better understand the molecular basis of cholangiocarcinoma, including the signaling pathways that contribute to tumor onset and progression. In this review, we discuss the genetic, molecular, and environmental factors that promote cholangiocarcinoma, emphasizing the role of the transforming growth factor β (TGFβ) signaling pathway in the progression of this cancer. We provide an overview of the physiological functions of TGFβ signaling in preserving liver homeostasis and describe how advanced cholangiocarcinoma benefits from the tumor-promoting effects of TGFβ. Moreover, we report the importance of noncoding RNAs as effector molecules downstream of TGFβ during cholangiocarcinoma progression, and conclude by highlighting the need for identifying novel and clinically relevant biomarkers for a better management of patients with cholangiocarcinoma.

scholarly journals MicroRNA-101a Inhibits Cardiac Fibrosis Induced by Hypoxia via Targeting TGFβRI on Cardiac Fibroblasts

2015 ◽  
Vol 35 (1) ◽  
pp. 213-226 ◽  
Author(s):  
Xin Zhao ◽  
Kejing Wang ◽  
Yuhua Liao ◽  
Qiutang Zeng ◽  
Yushu Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Transforming Growth Factor Beta ◽  
Cardiac Remodeling ◽  
Cardiac Fibrosis ◽  
Transforming Growth Factor ◽  
Cardiac Fibroblasts ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Luciferase Reporter ◽  
Migration Ability

Background/Aims: Hypoxia is a basic pathological challenge that is associated with numerous cardiovascular disorders including aberrant cardiac remodeling. Transforming growth factor beta (TGF-β) signaling pathway plays a pivotal role in mediating cardiac fibroblast (CF) function and cardiac fibrosis. Recent data suggested that microRNA-101a (miR-101a) exerted anti-fibrotic effects in post-infarct cardiac remodeling and improved cardiac function. This study aimed to investigate the potential relationship between hypoxia, miR-101a and TGF-β signaling pathway in CFs. Methods and Results: Two weeks following coronary artery occlusion in rats, the expression levels of both TGFβ1 and TGFβRI were increased, but the expression of miR-101a was decreased at the site of the infarct and along its border. Cultured rat neonatal CFs treated with hypoxia were characterized by the up-regulation of TGFβ1 and TGFβRI and the down-regulation of miR-101a. Delivery of miR-101a mimics significantly suppressed the expression of TGFβRI and p-Smad 3, CF differentiation and collagen content of CFs. These anti-fibrotic effects were abrogated by co-transfection with AMO-miR-101a, an antisense inhibitor of miR-101a. The repression of TGFβRI, a target of miR-101a, was validated by luciferase reporter assays targeting the 3'UTR of TGFβRI. Additionally, we found that overexpression of miR-101a reversed the improved migration ability of CFs and further reduced CF proliferation caused by hypoxia. Conclusion: Our study illustrates that miR-101a exerts anti-fibrotic effects by targeting TGFβRI, suggesting that miR-101a plays a multi-faceted role in modulating TGF-β signaling pathway and cardiac fibrosis.

Effect of High Glucose on Peritoneal Mesothelial Cell Biology

2000 ◽  
Vol 20 (2_suppl) ◽  
pp. 15-18 ◽  
Author(s):  
Hunjoo Ha ◽  
Hi Bahl Lee
Keyword(s):  
Protein Synthesis ◽  
Transforming Growth Factor Beta ◽  
High Glucose ◽  
Cell Biology ◽  
Transforming Growth Factor ◽  
Mesothelial Cell ◽  
Continuous Exposure ◽  
Messenger Rnas ◽  
Peritoneal Fibrosis ◽  
Peritoneal Mesothelial Cell

Objective This study reviews evidence that implicates high glucose (HG) in the pathogenesis of peritoneal fibrosis and proposes mechanisms potentially involved in the HG-induced peritoneal fibrosis that is observed in long-term peritoneal dialysis (PD) patients. Design Selected Western literature is reviewed, examining the effect of HG on rat or human peritoneal mesothelial cell (HPMC) biology with particular reference to extracellular matrix (ECM) gene expression and protein synthesis. Results HG up-regulated the expression of monocyte chemotactic peptide–1 (MCP-1), transforming growth factor beta 1 (TGFβ1), and fibronectin messenger RNAs (mRNAs) and proteins. These HG-induced up-regulations were effectively blocked by the inhibition of protein kinase C (PKC). In addition, cytosolic reactive oxygen species (ROS) rapidly increased in HPMC cultured under HG, and treatment with antioxidant effectively inhibited HG-induced fibronectin protein synthesis by HPMC. Conclusion Continuous exposure of the peritoneal membrane to HG may induce changes in HPMC biology, leading to excessive deposition of ECM and peritoneal injury. HG-induced activation of diacylglycerol PKC (DAG–PKC) plays a major role in up-regulation of MCP-1, TGFβ1, and fibronectin synthesis by HPMC cultured under HG. In addition, ROS, recently recognized as signalling molecules, are rapidly generated in HPMC as a result of increased glucose metabolism and may prove to be an important mediator of HG-induced peritoneal injury.

scholarly journals Gene Expression Profiling in Ovaries and Association Analyses Reveal HEP21 as a Candidate Gene for Sexual Maturity in Chickens

Animals ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 181
Author(s):  
Biao Chen ◽  
Guitao Liang ◽  
Xuenong Zhu ◽  
Yuwen Tan ◽  
Jiguo Xu ◽  
...  
Keyword(s):  
Candidate Gene ◽  
Transforming Growth Factor Beta ◽  
Sexual Maturity ◽  
Transforming Growth Factor ◽  
Age Of Onset ◽  
Thyroid Stimulating Hormone ◽  
Receptor Interaction ◽  
Ovary Development ◽  
Integrin Subunit ◽  
Association Analyses

The age of onset of sexual maturity is an important reproductive trait in chickens. In this study, we explored candidate genes associated with sexual maturity and ovary development in chickens. We performed DGE RNA-sequencing analyses of ovaries of pre-laying (P-F-O1, L-F-O1) and laying (P-F-O2, L-F-O2) hens of two sub-breeds of Ningdu Yellow chicken. A total of 3197 genes were identified in the two comparisons, and 966 and 1860 genes were detected exclusively in comparisons of P-F-O1 vs. P-F-O2 and L-F-O1 vs. L-F-O2, respectively. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that genes involved in transmembrane signaling receptor activity, cell adhesion, developmental processes, the neuroactive ligand–receptor interaction pathway, and the calcium signaling pathway were enriched in both comparisons. Genes on these pathways, including growth hormone (GH), integrin subunit beta 3 (ITGB3), thyroid stimulating hormone subunit beta (TSHB), prolactin (PRL), and transforming growth factor beta 3 (TGFB3), play indispensable roles in sexual maturity. As a gene unique to poultry, hen egg protein 21 kDa (HEP21) was chosen as the candidate gene. Differential expression and association analyses were performed. RNA-seq data and qPCR showed that HEP21 was significantly differentially expressed in pre-pubertal and pubertal ovaries. A total of 23 variations were detected in HEP21. Association analyses of single nucleotide polymorphisms (SNPs) in HEP21 and reproductive traits showed that rs315156783 was significantly related to comb height at 84 and 91 days. These results indicate that HEP21 is a candidate gene for sexual maturity in chickens. Our results contribute to a more comprehensive understanding of sexual maturity and reproduction in chickens.

scholarly journals Axolotl as a Model to Study Scarless Wound Healing in Vertebrates: Role of the Transforming Growth Factor Beta Signaling Pathway

2013 ◽  
Vol 2 (5) ◽  
pp. 250-260 ◽  
Author(s):  
Jean-François Denis ◽  
Mathieu Lévesque ◽  
Simon D. Tran ◽  
Aldo-Joseph Camarda ◽  
Stéphane Roy
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Growth Factor Beta

scholarly journals Does Porcine Oocytes Maturation in Vitro is Regulated by Genes Involved in Transforming Growth Factor Beta Receptor Signaling Pathway?

2017 ◽  
Vol 5 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Joanna Budna ◽  
Piotr Celichowski ◽  
Paresto Karimi ◽  
Wiesława Kranc ◽  
Artur Bryja ◽  
...  
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Oocyte Growth ◽  
Maturation In Vitro ◽  
Differential Expression Pattern ◽  
Before And After ◽  
Growth Factor Beta

Summary The oocyte growth and development in follicular environment are substantially accompanied by surrounding somatic cumulus (CCs) and granulosa cells (GCs). During these processes, the mammalian gametes reach full maturational stage and may be further successfully fertilized by single spermatozoon. These unique mechanisms are regulated by expression of clusters of genes and their biochemical signaling pathways. In this article we described differential expression pattern of transforming growth factor beta (TGFB) gene superfamily in porcine oocytes before and after in vitro maturation (IVM). We performed Affymetrix® microarray assays to investigate the TGFB-related genes expression profile in porcine immature oocytes and gametes cultured for 44h in vitro. In results we found 419 different genes, 379 genes with lower expression, and 40 genes characterized by increased RNA profile. Moreover, significant up-regulation of 6 genes belonging to TGFB signaling pathway such as: TGFBR3, SMAD4, FOS, KLF10, ID1, MAP3K1 in immature porcine oocytes (before IVM), was also observed. It may be suggested that genes involved in TGFB-related signaling pathway are substantially regulated before IVM. Furthermore, these genes may play a significant role during early stages of nuclear and/or cytoplasmic porcine oocytes maturation. The investigated transcripts may be also recommended as the markers of oocytes maturational capability in pigs.

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