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https://www.readbyqxmd.com/read/28806736/unravelling-the-interplay-of-sphingolipids-and-tgf-%C3%AE-signaling-in-the-human-corneal-stroma
#1
Sarah E Nicholas, Tyler G Rowsey, Shrestha Priyadarsini, Nawajes A Mandal, Dimitrios Karamichos
PURPOSE: To delineate the role of Sphingolipids (SPLs) in the human cornea and their cross-talks with transforming growth factor beta (TGF-β) in order to develop novel, non-invasive therapies. METHODS: Human corneal fibroblasts (HCFs) were harvested from healthy donors, stimulated with Vitamin C to promote extracellular matrix assembly, treated with exogenous sphingosine-1-phosphate (S1P) or sphingosine kinase inhibitor 2 (SPHK I2) and isolated after 4 weeks for further analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28805491/intermedin-inhibits-unilateral-ureteral-obstruction-induced-oxidative-stress-via-nadph-oxidase-nox4-and-camp-dependent-mechanisms
#2
Xi Qiao, Lihua Wang, Yanhong Wang, Xiaole Su, Yue Qi, Yun Fan, Zhiqiang Peng
NADPH oxidase Nox4-derived reactive oxygen species (ROS) play important roles in renal fibrosis. Our previous study demonstrated that intermedin (IMD) alleviated unilateral ureteral obstruction (UUO)-induced renal fibrosis by inhibition of ROS. However, the precise mechanisms remain unclear. Herein, we investigated the effect of IMD on Nox4 expression and NADPH oxidase activity in rat UUO model, and explored if these effect were achieved through cAMP-PKA pathway, the important post-receptor signal transduction pathway of IMD, in TGF-β1-stimulated rat proximal tubular cell (NRK-52E)...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28805484/disparate-phospho-smad2-levels-in-advanced-type-2-diabetes-patients-with-diabetic-nephropathy-and-early-experimental-db-db-mouse-model
#3
Lise Høj Thomsen, Morten Fog-Tonnesen, Lisbeth Nielsen Fink, Jenny Norlin, Amaya García de Vinuesa, Troels Krarup Hansen, Emile de Heer, Peter Ten Dijke, Alexander Rosendahl
Uncontrolled activation of transforming growth factor beta (TGF-β) family members is hypothesized to participate in type 2 diabetes (T2D) dependent diabetic nephropathy (DN). We evaluated and compared downstream activation of the Smad2-signaling pathway in kidney samples from T2D patients to kidneys from the T2D model of leptin receptor deficient db/db mouse. Furthermore, expression of TGF-β family members was evaluated to elucidate molecular mechanisms in the mouse model. Kidney samples from patients with advanced stages of DN showed elevated pSmad2 staining whereas db/db mouse kidneys surprisingly showed a decrease in pSmad2 in the tubular compartment...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28804991/nf-%C3%AE%C2%BAb2-controls-migratory-activity-of-memory-t-cells-by-regulating-expression-of-cxcr4-in-a-mouse-model-of-sj%C3%A3-gren-s-syndrome
#4
Mie Kurosawa, Rieko Arakaki, Akiko Yamada, Takaaki Tsunematsu, Yasusei Kudo, Jonathan Sprent, Naozumi Ishimaru
OBJECTIVE: Dysregulated chemokine signaling contributes to autoimmune diseases by facilitating aberrant T-cell infiltration into target tissues, but the specific chemokines, receptors, and T-cell populations remain largely unidentified. Role of the potent chemokine CXCL12 and its receptor CXCR4 in T-cell autoimmune response was examined using alymphoplasia (aly)/aly mice, a Sjögren's syndrome (SS) model. METHODS: T-cell phenotypes in the salivary gland of aly/aly mice were evaluated using immunological analysis...
August 13, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28804566/microrna-93-inhibits-apoptosis-and-promotes-proliferation-invasion-and-migration-of-renal-cell-carcinoma-achn-cells-via-the-tgf-%C3%AE-smad-signaling-pathway-by-targeting-runx3
#5
Li-Jie Liu, Jian-Jun Yu, Xiao-Lin Xu
We investigated the ability of microRNA-93 (miR-93) to influence proliferation, invasion, migration, and apoptosisofrenal cell carcinoma (RCC) cells via transforming growth factor-β/solvated metal atom dispersed (TGF-β/Smad) signaling by targeting runt-related transcription factor 3 (RUNX3). RCC tissues with corresponding adjacent normal tissues were collected from 249 RCC patients. And normal renal tissues were collected from patients without RCC who received nephrectomy. The RCC cell line ACHN was treated with miR-93 mimic, mimic-negative control (NC), miR-93 inhibitor, inhibitor-NC, and miR-93 inhibitor + small interfering RNA (siRNA) against RUNX3 (si-RUNX3)...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28804546/ccr7-enhances-the-angiogenic-capacity-of-esophageal-squamous-carcinoma-cells-in-vitro-via-activation-of-the-nf-%C3%AE%C2%BAb-vegf-signaling-pathway
#6
Qing-Yong Cai, Gui-You Liang, Yi-Feng Zheng, Qun-You Tan, Ru-Wen Wang, Kun Li
High levels of angiogenesis are associated with poor prognosis and a highly invasive phenotype in esophageal squamous carcinoma. C-C chemokine receptor type 7 (CCR7) is overexpressed in multiple tumor types and has been suggested to act as an oncogene and pro-angiogenic factor. This study aimed to elucidate the effect of CCR7 on the angiogenic capacity of esophageal squamous carcinoma cells in vitro. Expression of CCR7 in esophageal squamous carcinoma cell lines and normal human esophageal epithelial cell line was examined by western blotting and quantitative real-time PCR...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28804544/sirt3-attenuates-angii-induced-cardiac-fibrosis-by-inhibiting-myofibroblasts-transdifferentiation-via-stat3-nfatc2-pathway
#7
Xiaobin Guo, Fangying Yan, Jingyuan Li, Chunmei Zhang, Peili Bu
Cardiac fibrosis is a maladaptive response to various stresses, characterized by increased interstitial collagen deposition and progressive cardiac dysfunction. The transdifferentiation of fibroblasts into myofibroblasts is an essential process in the pathogenesis of cardiac fibrosis. SIRT3, as a mitochondrial NAD(+)-dependent histone deacetylase, has been demonstrated beneficial in many cardiovascular diseases. However, the specific mechanism of its protective role in cardiac fibrosis needs to be elucidated further...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28804523/tri-methylation-of-h3k79-is-decreased-in-tgf-%C3%AE-1-induced-epithelial-to-mesenchymal-transition-in-lung-cancer
#8
Emilie Evanno, Julie Godet, Nathalie Piccirilli, Joëlle Guilhot, Serge Milin, Jean Marc Gombert, Benoit Fouchaq, Joëlle Roche
BACKGROUND: The epithelial-to-mesenchymal transition (EMT) enables epithelial cancer cells to acquire mesenchymal features and contributes to metastasis and resistance to treatment. This process involves epigenetic reprogramming for gene expression. We explored global histone modifications during TGF-β1-induced EMT in two non-small cell lung cancer (NSCLC) cell lines and tested different epigenetic treatment to modulate or partially reverse EMT. RESULTS: Loss of classical epithelial markers and gain of mesenchymal markers were verified in A549 and H358 cell lines during TGF-β1-induced EMT...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28803990/high-doses-of-baicalin-induces-kidney-injury-and-fibrosis-through-regulating-tgf-%C3%AE-smad-signaling-pathway
#9
Yi Cai, Wanqing Ma, Yichuan Xiao, Bo Wu, Xiaobing Li, Fengrong Liu, Jianhua Qiu, Genshui Zhang
Baicalin is a major flavonoid compound purified from Scutellariae radix, which has been described as an herb in the Chinese Pharmacopoeia. Previous studies have suggested baicalin possessed extensive anti-inflammatory, anti-cancer, anti-viral properties. However, up to known, there have been no reports of safety and toxicity in the rats following oral administration of baicalin. In this present study, we showed the first evidence that treatment of baicalin (400, 800 and 1600mg/kg/day) induced significantly kidney injury and fibrosis...
August 10, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28803696/differential-modulation-of-glial-cell-mediated-neuroinflammation-in-plasmodium-berghei-anka-infection-by-tgf-%C3%AE-and-il-6
#10
Samrat Sarkar, Tarun Keswani, Anirban Sengupta, Soham Mitra, Arindam Bhattacharyya
Modulation of pro-inflammatory and anti-inflammatory axis and orientation of glial cell function towards neuroinflammation, were hallmark signs of cerebral malaria (CM). CM pathogenesis was concerned with the circulating levels of Interleukin 6 (IL 6) and Transforming growth factor β (TGF β). Definite roles of these two cytokines in brain related pathology remained largely unexplored. To study the effect of these two cytokines, we have examined changes in morphology and in activation profile of the glial cells after TGF β and IL 6 neutralization during CM in cortex and cerebellum of the Plasmodium berghei ANKA (PbA) infected male swiss albino mice...
August 10, 2017: Cytokine
https://www.readbyqxmd.com/read/28802663/peripheral-gamma-delta-t-cells-secrete-inflammatory-cytokines-in-women-with-idiopathic-recurrent-pregnancy-loss
#11
Ayantika Talukdar, Reeta Rai, K Aparna Sharma, D N Rao, Alpana Sharma
BACKGROUND: Gamma delta (γδ) T cells are known to link innate and adaptive immunity. Decidual γδ T cells are known to provide immunotolerance by producing IL-10 and TGF-β. In recurrent pregnancy loss (RPL) females, the role of peripheral γδ T cells remain unstudied. OBJECTIVE: To investigate the different phenotypes of γδ T cells in the peripheral blood of women with idiopathic RPL and their possible involvement in RPL condition. METHODS: A total of 120 women were recruited for the study...
August 9, 2017: Cytokine
https://www.readbyqxmd.com/read/28802561/recombinant-human-elafin-promotes-alveologenesis-in-newborn-mice-exposed-to-chronic-hyperoxia
#12
Wenli Han, Xiaomei Li, Han Zhang, Benli Yu, Chunbao Guo, Chun Deng
BACKGROUND/AIMS: Elastase inhibitors reverse elastin degradation and abnormal alveologenesis and attenuate the lung structural abnormalities induced by mechanical ventilation with O2-rich gas. The potential of these molecules to improve endothelial function and to ameliorate severe bronchopulmonary dysplasia (BPD) during lung development is not yet understood. We sought to determine whether the intratracheal treatment of newborn mice with the elastase inhibitor elafin would prevent hyperoxia-induced lung elastin degradation and the cascade of events that cause abnormal alveologenesis...
August 9, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28802359/transmission-analysis-of-tgfb1-gene-polymorphisms-in-non-syndromic-cleft-lip-with-or-without-cleft-palate
#13
Ginila T Raju, Bhaskar V K S Lakkakula, Jyotsna Murthy, Munirajan Arasambattu Kannan, Solomon F D Paul
OBJECTIVES: Transforming growth factor beta1 (TGF-β1) plays a significant role in craniofacial development. Previous linkage studies reported that the TGF-β1-locus at 19q13.1 harbour predisposing genes for non-syndromic oral clefts. In the present study case parents triads were evaluated to find the transmission effects of genetic variants in TGF- β1 towards non-syndromic cleft lip or palate (NSCL/P). METHODS: Using allelic discrimination method148 families (case-parent triads) were assessed for single nucleotide polymorphisms (SNPs) in TGF-β1 gene...
September 2017: International Journal of Pediatric Otorhinolaryngology
https://www.readbyqxmd.com/read/28802229/tgf-%C3%AE-mediated-repression-of-mst1-by-dnmt1-promotes-glioma-malignancy
#14
Zhifei Guo, Guangyuan Li, Erbao Bian, Chun-Chun Ma, Jinghai Wan, Bing Zhao
Human gliomas are related to high rates of morbidity and mortality. TGF-β promotes the growth of glioma cells, and correlate with the degree of malignancy of human gliomas. However, the molecular mechanisms involved in the malignant function of TGF-β are not fully elucidated. Here, we showed that TGF-β induced the downregulation of MST1 expression in U87 and U251 glioma cells. Treatment of glioma cells with the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-AzadC) prevented the loss of MST1 expression...
August 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28802065/quercetin-reverses-experimental-cirrhosis-by-immunomodulation-of-the-proinflammatory-and-profibrotic-processes
#15
Sael Casas-Grajales, Luis F Vázquez-Flores, Erika Ramos-Tovar, Erika Hernández-Aquino, Rosa E Flores-Beltrán, Carlos M Cerda-García-Rojas, Javier Camacho, Mineko Shibayama, Víctor Tsutsumi, Pablo Muriel
The ability of quercetin to reverse an established cirrhosis has not yet been investigated. Therefore, the aim of the present study was to examine the efficacy of this flavonoid in reversing experimental cirrhosis. Cirrhosis was induced by intraperitoneal administration of TAA (200 mg/kg of body weight) three times per week for 8 weeks or by intraperitoneal petrolatum-CCl4 (400 mg/kg of body weight) administration three times per week for 8 weeks. To determine the capacity of quercetin to prevent liver fibrosis, the flavonoid (50 mg/kg of body weight, p...
August 12, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28802000/pmepa1-induced-by-rankl-p38-mapk-pathway-has-a-novel-role-in-osteoclastogenesis
#16
Noboru Funakubo, Xianghe Xu, Toshio Kukita, Seiji Nakamura, Hiroshi Miyamoto, Akiko Kukita
Osteoclasts are multinucleated cells formed by fusion of preosteoclasts (POCs) derived from cells of the monocyte/macrophage lineage. We have reported a culture system that supports the formation of POCs from stroma-depleted rat bone marrow cells. Global gene expression analysis of this culture system identified genes highly expressed in POCs. Here, we have analyzed the expression and function of one of these highly expressed genes, prostate transmembrane protein androgen induced 1 (Pmepa1), a target of TGF-β and binds Nedd4 ubiquitin ligase, which plays a role in intracellular trafficking...
August 12, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28801914/blockade-of-transforming-growth-factor-%C3%AE-signaling-enhances-oncolytic-herpes-simplex-virus-efficacy-in-patient-derived-recurrent-glioblastoma-models
#17
Shinichi Esaki, Fares Nigim, Esther Moon, Samantha Luk, Juri Kiyokawa, William Curry, Daniel P Cahill, Andrew S Chi, A John Iafrate, Robert L Martuza, Samuel D Rabkin, Hiroaki Wakimoto
Despite the current standard of multimodal management, glioblastoma (GBM) inevitably recurs and effective therapy is not available for recurrent disease. A subset of tumor cells with stem-like properties, termed GBM stem-like cells (GSCs), are considered to play a role in tumor relapse. Although oncolytic herpes simplex virus (oHSV) is a promising therapeutic for GBM, its efficacy against recurrent GBM is incompletely characterized. Transforming growth factor beta (TGF-β) plays vital roles in maintaining GSC stemness and GBM pathogenesis...
August 12, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28801702/paeonol-attenuates-aging-mrc-5-cells-and-inhibits-epithelial-mesenchymal-transition-of-premalignant-hacat-cells-induced-by-aging-mrc-5-cell-conditioned-medium
#18
Lihua Yang, Shangping Xing, Kun Wang, Hua Yi, Biaoyan Du
Senescence-associated secretory phenotype (SASP) factors, such as IL-6 and IL-8, are extremely critical in tissue microenvironment. Senescent human fibroblasts facilitate epithelial-mesenchymal transition (EMT) in premalignant epithelial cells mainly through the secretion of SASP factors. Meanwhile, premalignant human HaCaT Keratinocyte (HaCaT) cells as immortal epithelial cells are susceptible to malignant transformation. Paeonol, an herbal phenolic component found in peonies, exerts anti-aging and anti-tumor efficacies, while the molecular mechanisms of paeonol on EMT in premalignant HaCaT cells induced by SASP factors are unclear...
August 12, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28801346/pan-ppar-agonist-iva337-is-effective-in-experimental-lung-fibrosis-and-pulmonary-hypertension
#19
Jerome Avouac, Irena Konstantinova, Christophe Guignabert, Sonia Pezet, Jeremy Sadoine, Thomas Guilbert, Anne Cauvet, Ly Tu, Jean-Michel Luccarini, Jean-Louis Junien, Pierre Broqua, Yannick Allanore
OBJECTIVE: To evaluate the antifibrotic effects of the pan-peroxisome proliferator-activated receptor (PPAR) agonist IVA337 in preclinical mouse models of pulmonary fibrosis and related pulmonary hypertension (PH). METHODS: IVA337 has been evaluated in the mouse model of bleomycin-induced pulmonary fibrosis and in Fra-2 transgenic mice, this latter being characterised by non-specific interstitial pneumonia and severe vascular remodelling of pulmonary arteries leading to PH...
August 11, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28801277/-pioglitazone-ameliorates-atherosclerosis-in-apoe-knockout-mice-through-transforming-growth-factor-%C3%AE-smad-signaling-and-adaptive-t-cell-immunity
#20
Yu-Ling Tian, Li-Jun Wang, Yue Wu, Wei-Ping Zhang, Xiao Liang, Zu-Yi Yuan
OBJECTIVE: To examine whether transforming growth factor-β (TGF-β) pathway and adaptive T cell immunity play roles in the anti-atherosclerotic effects of pioglitazone (PIO) in ApoE(-/-) mice. METHODS: ApoE(-/-) mice with atherosclerosis induced by high-fat feeding were treated daily with PIO (20 mg/kg) or vehicle for 8 weeks. The protein expressions of TGF-β pathway in the atheromatous lesions of the aorta and the percentages of IFN-γ(+) and Foxp3(+) cells in the spleen of the mice were examined with immunohistochemical staining...
August 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
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