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Nrf2 AND Tgf beta

Venkatachalam Sukumaran, Se Chang Park, Sib Sankar Giri
This study evaluated the effects of ginger (Zingiber officinale) as a feeding supplement on the growth, skin mucus immune parameters, and cytokine-related gene expression of Labeo rohita, and its susceptibility to Aeromonas hydrophila infection. Diets containing six different concentrations of dried ginger (0% [basal diet], 0.2% [G2], 0.4% [G4], 0.6% [G6], 0.8% [G8], and 1.0% [G10] were fed to fish (average weight: 12.3 g) for 60 days. Growth parameters were examined at 30 and 60 days post-feeding. Skin mucosal immune responses and gene expression were examined 60 days post-feeding...
October 2016: Fish & Shellfish Immunology
Geeske Genrich, Marcus Kruppa, Lennart Lenk, Ole Helm, Anna Broich, Sandra Freitag-Wolf, Christoph Röcken, Bence Sipos, Heiner Schäfer, Susanne Sebens
BACKGROUND: Nuclear factor E2 related factor-2 (Nrf2) is an oxidative stress inducible transcription factor being essential in regulating cell homeostasis. Thus, acute induction of Nrf2 in epithelial cells exposed to inflammation confers protection from oxidative cell damage and mutagenesis supporting an anti-tumorigenic role for Nrf2. However, pancreatic ductal adenocarcinoma (PDAC) is characterized by persistent Nrf2 activity conferring therapy resistance which points to a pro-tumorigenic role of Nrf2...
2016: BMC Cancer
Naoki Oshimori, Daniel Oristian, Elaine Fuchs
Subsets of long-lived, tumor-initiating stem cells often escape cancer therapies. However, sources and mechanisms that generate tumor heterogeneity and drug-resistant cell population are still unfolding. Here, we devise a functional reporter system to lineage trace and/or genetic ablate signaling in TGF-β-activated squamous cell carcinoma stem cells (SCC-SCs). Dissecting TGF-β's impact on malignant progression, we demonstrate that TGF-β concentrating near tumor-vasculature generates heterogeneity in TGF-β signaling at tumor-stroma interface and bestows slower-cycling properties to neighboring SCC-SCs...
February 26, 2015: Cell
Viranuj Sueblinvong, Victor Tseng, Tierra Smith, Ramin Saghafi, Stephen T Mills, David C Neujahr, David M Guidot
BACKGROUND: Chronic alcohol ingestion induces the expression of transforming growth factor beta-1(TGFβ1), inhibits nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated activation of the antioxidant response element (ARE), depletes alveolar glutathione pools, and potentiates acute lung injury. In this study, we examined the mechanistic relationship between TGFβ1 and Nrf2-ARE signaling in the experimental alcoholic lung. METHODS: Wild-type mice were treated ± alcohol in drinking water for 8 weeks and their lungs were assessed for Nrf2 expression...
November 2014: Alcoholism, Clinical and Experimental Research
Nina Queisser, Kathrin Happ, Samuel Link, Daniel Jahn, Anna Zimnol, Andreas Geier, Nicole Schupp
Mineralocorticoid receptor blockers show antifibrotic potential in hepatic fibrosis. The mechanism of this protective effect is not known yet, although reactive oxygen species seem to play an important role. Here, we investigated the effects of elevated levels of aldosterone (Ald), the primary ligand of the mineralocorticoid receptor, on livers of rats in a hyperaldosteronism model: aldosterone-induced hypertension. Male Sprague-Dawley rats were treated for 4 weeks with aldosterone. To distinguish if damage caused in the liver depended on increased blood pressure or on increased Ald levels, the mineralocorticoid receptor antagonist spironolactone was given in a subtherapeutic dose, not normalizing blood pressure...
November 1, 2014: Toxicology and Applied Pharmacology
Chenlin Gao, Wei Huang, Keizo Kanasaki, Yong Xu
Diabetic nephropathy (DN) is a common and characteristic microvascular complication of diabetes; the mechanisms that cause DN have not been clarified, and the epigenetic mechanism was promised in the pathology of DN. Furthermore, ubiquitination and small ubiquitin-like modifier (SUMO) were involved in the progression of DN. MG132, as a ubiquitin proteasome, could improve renal injury by regulating several signaling pathways, such as NF- κ B, TGF- β , Nrf2-oxidative stress, and MAPK. In this review, we summarize how ubiquitination and sumoylation may contribute to the pathology of DN, which may be a potential treatment strategy of DN...
2014: BioMed Research International
Michael W Epperly, J Richard Chaillet, Ronny Kalash, Ben Shaffer, Julie Goff, Darcy Franicola, Xichen Zhang, Tracy Dixon, Frank Houghton, Hong Wang, Hebist Berhane, Cynthia Romero, Jee-Hong Kim, Joel S Greenberger
Mitochondrial targeted manganese superoxide dismutase is a major antioxidant enzyme, the levels of which modulate the response of cells, tissues and organs to ionizing irradiation. We developed a Tet-regulated MnSOD mouse (MnSOD(tet)) to examine the detailed relationship between cellular MnSOD concentration and radioresistance and carried out in vitro studies using bone marrow culture derived stromal cell lines (mesenchymal stem cells). Homozygous MnSOD(tet/tet) cells had low levels of MnSOD, reduced viability and proliferation, increased radiosensitivity, elevated overall antioxidant stores, and defects in cell proliferation and DNA strand-break repair...
August 2013: Radiation Research
Sixiang You, Eri Nakanishi, Hiroko Kuwata, Jihua Chen, Yasushi Nakasone, Xi He, Jianhua He, Xiangxin Liu, Shirui Zhang, Bin Zhang, De-Xing Hou
SCOPE: Garlic is used for both culinary and medicinal purposes by many cultures. The garlic organosulfur compounds (GOSCs) are thought to be bioactive components. This study aims to clarify the antiinflammatory effects and molecular mechanisms of GOSCs in both cell and animal models. METHODS AND RESULTS: RAW264.7 cells were treated with six kinds of GOSCs to screen their influence on cyclooxygenase-2 and inducible nitric oxide synthase expression by Western blotting...
November 2013: Molecular Nutrition & Food Research
Yukari Okita, Atsushi Kamoshida, Hiroyuki Suzuki, Ken Itoh, Hozumi Motohashi, Kazuhiko Igarashi, Masayuki Yamamoto, Tomohiro Ogami, Daizo Koinuma, Mitsuyasu Kato
Transforming growth factor-β (TGF-β) has multiple functions in embryogenesis, adult homeostasis, tissue repair, and development of cancer. Here, we report that TGF-β suppresses the transcriptional activation of the heme oxygenase-1 (HO-1) gene, which is implicated in protection against oxidative injury and lung carcinogenesis. HO-1 is a target of the oxidative stress-responsive transcription factor Nrf2. TGF-β did not affect the stabilization or nuclear accumulation of Nrf2 after stimulation with electrophiles...
July 12, 2013: Journal of Biological Chemistry
José Pablo Vázquez-Medina, José G Soñanez-Organis, Ruben Rodriguez, Jose A Viscarra, Akira Nishiyama, Daniel E Crocker, Rudy M Ortiz
Elephant seals naturally experience prolonged periods of absolute food and water deprivation (fasting). In humans, rats and mice, prolonged food deprivation activates the renin-angiotensin system (RAS) and increases oxidative damage. In elephant seals, prolonged fasting activates RAS without increasing oxidative damage likely due to an increase in antioxidant defenses. The mechanism leading to the upregulation of antioxidant defenses during prolonged fasting remains elusive. Therefore, we investigated whether prolonged fasting activates the redox-sensitive transcription factor Nrf2, which controls the expression of antioxidant genes, and if such activation is potentially mediated by systemic increases in RAS...
August 1, 2013: Journal of Experimental Biology
Min-Kyung Choi, Jong-Min Han, Hyeong-Geug Kim, Jin-Suk Lee, Jong-Suk Lee, Jing-Hua Wang, Seung-Wan Son, Hye-Jung Park, Chang-Gue Son
ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia capillaris, also called "InJin" in Korean, has been widely used to treat various hepatic disorders in traditional Oriental medicine. AIMS: The purpose of this study is to evaluate the hepatoprotective effect of Artemisia capillaris (aqueous extract, WAC) on alcoholic liver injury. MATERIALS AND METHODS: Liver injury was induced by oral administration of 30% alcohol (10 mL/kg, twice per day) plus pyrazole (PRZ, 30 mg/kg) with/without WAC (50, 100mg/kg, orally once per day) or silymarin (50mg/kg) for 10 days...
June 3, 2013: Journal of Ethnopharmacology
Palanivel Chitra, Gowrikumar Saiprasad, Ramar Manikandan, Ganapasam Sudhandiran
Idiopathic pulmonary fibrosis (IPF) is a progressive, debilitating and fatal lung disorder with high mortality rate. Unfortunately, to date the treatment for IPF remains unsatisfying and in severe cases lung transplantations are performed as a therapeutic measure. Thus, it becomes great interest to find novel agents to treat IPF. Berberine, a plant alkaloid known for its broad pharmacological activities remains a remedy against multiple diseases. This study was hypothesized to investigate the antifibrotic potential of berberine against bleomycin-induced lung injury and fibrosis, a tentative animal model...
May 23, 2013: Toxicology Letters
Lingling Yang, Mingli Qu, Yao Wang, Haoyun Duan, Peng Chen, Ye Wang, Weiyun Shi, Patrik Danielson, Qingjun Zhou
Trichostatin A (TSA) has been shown to prevent fibrosis in vitro and in vivo. The present study aimed at investigating the role of reactive oxygen species (ROS) scavenging by TSA on transforming growth factor-β (TGF-β)-induced myofibroblast differentiation of corneal fibroblasts in vitro. Human immortalized corneal fibroblasts were treated with TGF-β in the presence of TSA, the NAD(P)H oxidase inhibitor diphenyleneiodonium (DPI), the antioxidant N-acetyl-cysteine (NAC), the NF-E2-related factor 2-antioxidant response element (Nrf2-ARE) activator sulforaphane, or small interfering RNA...
March 2013: Molecular Pharmacology
Chang Joo Oh, Joon-Young Kim, Young-Keun Choi, Han-Jong Kim, Ji-Yun Jeong, Kwi-Hyun Bae, Keun-Gyu Park, In-Kyu Lee
TGF-β plays a key role in the development of renal fibrosis. Suppressing the TGF-β signaling pathway is a possible therapeutic approach for preventing this disease, and reports have suggested that Nrf2 protects against renal fibrosis by inhibiting TGF-β signaling. This study examines whether dimethylfumarate (DMF), which stimulates Nrf2, prevents renal fibrosis via the Nrf2-mediated suppression of TGF-β signaling. Results showed that DMF increased nuclear levels of Nrf2, and both DMF and adenovirus-mediated overexpression of Nrf2 (Ad-Nrf2) decreased PAI-1, alpha-smooth muscle actin (α-SMA), fibronectin and type 1 collagen expression in TGF-β-treated rat mesangial cells (RMCs) and renal fibroblast cells (NRK-49F)...
2012: PloS One
Elise Artaud-Macari, Delphine Goven, Stéphanie Brayer, Akila Hamimi, Valérie Besnard, Joëlle Marchal-Somme, Zeina El Ali, Bruno Crestani, Saadia Kerdine-Römer, Anne Boutten, Marcel Bonay
AIMS: Oxidants have been implicated in the pathophysiology of idiopathic pulmonary fibrosis (IPF), especially in myofibroblastic differentiation. We aimed at testing the hypothesis that nuclear factor erythroid 2-related factor 2 (Nrf2), the main regulator of endogenous antioxidant enzymes, is involved in fibrogenesis via myofibroblastic differentiation. Fibroblasts were cultured from the lungs of eight controls and eight IPF patients. Oxidants-antioxidants balance, nuclear Nrf2 expression, and fibroblast phenotype (α-smooth muscle actin and collagen I expression, proliferation, migration, and contraction) were studied under basal conditions and after Nrf2 knockdown or activation by Nrf2 or Keap1 siRNA transfection...
January 1, 2013: Antioxidants & Redox Signaling
Won Dong Kim, Young Woo Kim, Il Je Cho, Chang Ho Lee, Sang Geon Kim
Nrf2 has an anti-carcinogenic effect. However, an increase in Nrf2 activity is also implicated in cancer chemoresistance. A switch from E-cadherin to N-cadherin affects the transdifferentiation and metastasis of cancer cells. In view of the key role of this switch in cancer malignancy, we investigated the regulatory effect of E-cadherin on Nrf2. In HEK293 cells, overexpression of E-cadherin inhibited the nuclear accumulation of Nrf2, and prevented Nrf2-dependent gene induction. GST pull-down and immunocytochemical assays verified the interaction between E-cadherin and Nrf2: E-cadherin bound the C-terminus of Nrf2, but not its N-terminus, which comprises the Neh2 domain responsible for phosphorylation of Ser40...
March 1, 2012: Journal of Cell Science
Chang Joo Oh, Joon-Young Kim, Ae-Kyung Min, Keun-Gyu Park, Robert A Harris, Han-Jong Kim, In-Kyu Lee
Sulforaphane (SFN) is a dietary isothiocyanate that exerts chemopreventive effects via NF-E2-related factor 2 (Nrf2)-mediated induction of antioxidant/phase II enzymes, such as heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). This work was undertaken to evaluate the effects of SFN on hepatic fibrosis and profibrotic transforming growth factor (TGF)-β/Smad signaling, which are closely associated with oxidative stress. SFN suppressed TGF-β-enhanced expression of α-smooth muscle actin (α-SMA), a marker of hepatic stellate cell (HSC) activation, and profibrogenic genes such as type I collagen, fibronectin, tissue inhibitor of matrix metalloproteinase (TIMP)-1, and plasminogen activator inhibitor (PAI)-1 in hTERT, an immortalized human HSC line...
February 1, 2012: Free Radical Biology & Medicine
Charalambos Michaeloudes, Po-Jui Chang, Mario Petrou, Kian Fan Chung
RATIONALE: Aberrant airway smooth muscle cell (ASMC) function and overexpression of transforming growth factor (TGF)-β, which modulates ASMC proliferative and inflammatory function and induces oxidant release, are features of asthma. Nuclear factor E2-related factor 2 (Nrf2) activates antioxidant genes conferring protection against oxidative stress. OBJECTIVES: To determine the role of Nrf2 in ASMCs and its modulation by TGF-β, and compare Nrf2 activity in ASMCs from subjects with severe and nonsevere asthma and healthy subjects...
October 15, 2011: American Journal of Respiratory and Critical Care Medicine
Elizabeth L Travis, Girish Rachakonda, Xinhui Zhou, Katrina Korhonen, Konjeti R Sekhar, Swati Biswas, Michael L Freeman
Subsets of cancer survivors who have been subjected to thoracic irradiation face the prospect of developing pulmonary injury. Radiation-induced pulmonary fibrosis is an insidious injury that presents 6 to 24 months after irradiation and continues to progress over a period of years. TGF-β and reactive oxygen species contribute significantly to the pathogenesis of this injury. The transcription factor NRF2 controls antioxidant gene expression and therefore regulates the cellular oxidant burden. This work demonstrates an additional paradigm for NRF2: suppression of TGF-β-mediated signaling, assessed by measuring expression of a surrogate TGF-β1 target gene (PAI-1) in lung fibroblasts...
September 15, 2011: Free Radical Biology & Medicine
Su Jin Kang, Aram You, Mi-Kyoung Kwak
Angiotensin II (ATII), a physiologically active mediator of the renin-angiotensin system, has been shown to be associated with renal fibrosis pathophysiology. In our current study with murine renal epithelial TCMK-1 cells, ATII inhibited the expression of NF-E2-related factor 2 (Nrf2)-target antioxidant genes such as NAD(P)H: quinone oxidoreductase-1 and γ-glutamate cysteine ligase (GCL). In accord to the reduced expression of GCL, a GSH biosynthesis enzyme, ATII treatment reduced intracellular GSH content and increased the levels of reactive oxygen species (ROS)...
May 2011: Archives of Pharmacal Research
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