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https://www.readbyqxmd.com/read/28339457/targeted-aav5-smad7-gene-therapy-inhibits-corneal-scarring-in-vivo
#1
Suneel Gupta, Jason T Rodier, Ajay Sharma, Elizabeth A Giuliano, Prashant R Sinha, Nathan P Hesemann, Arkasubhra Ghosh, Rajiv R Mohan
Corneal scarring is due to aberrant activity of the transforming growth factor β (TGFβ) signaling pathway following traumatic, mechanical, infectious, or surgical injury. Altered TGFβ signaling cascade leads to downstream Smad (Suppressor of mothers against decapentaplegic) protein-mediated signaling events that regulate expression of extracellular matrix and myogenic proteins. These events lead to transdifferentiation of keratocytes into myofibroblasts through fibroblasts and often results in permanent corneal scarring...
2017: PloS One
https://www.readbyqxmd.com/read/28337147/3d-proximal-tubule-tissues-recapitulate-key-aspects-of-renal-physiology-to-enable-nephrotoxicity-testing
#2
Shelby M King, J William Higgins, Celina R Nino, Timothy R Smith, Elizabeth H Paffenroth, Casey E Fairbairn, Abigail Docuyanan, Vishal D Shah, Alice E Chen, Sharon C Presnell, Deborah G Nguyen
Due to its exposure to high concentrations of xenobiotics, the kidney proximal tubule is a primary site of nephrotoxicity and resulting attrition in the drug development pipeline. Current pre-clinical methods using 2D cell cultures and animal models are unable to fully recapitulate clinical drug responses due to limited in vitro functional lifespan, or species-specific differences. Using Organovo's proprietary 3D bioprinting platform, we have developed a fully cellular human in vitro model of the proximal tubule interstitial interface comprising renal fibroblasts, endothelial cells, and primary human renal proximal tubule epithelial cells to enable more accurate prediction of tissue-level clinical outcomes...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28335481/genetic-variants-contributing-to-colistin-cytotoxicity-identification-of-tgif1-and-hoxd10-using-a-population-genomics-approach
#3
Michael T Eadon, Ronald J Hause, Amy L Stark, Ying-Hua Cheng, Heather E Wheeler, Kimberly S Burgess, Eric A Benson, Patrick N Cunningham, Robert L Bacallao, Pierre C Dagher, Todd C Skaar, M Eileen Dolan
Colistin sulfate (polymixin E) is an antibiotic prescribed with increasing frequency for severe Gram-negative bacterial infections. As nephrotoxicity is a common side effect, the discovery of pharmacogenomic markers associated with toxicity would benefit the utility of this drug. Our objective was to identify genetic markers of colistin cytotoxicity that were also associated with expression of key proteins using an unbiased, whole genome approach and further evaluate the functional significance in renal cell lines...
March 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28332739/gdf9-affects-the-development-and-tight-junction-functions-of-immature-bovine-sertoli-cells
#4
K Tang, L Wang, Y Jin, W Yang, L Yang
Transforming growth factor-β (TGFβ) superfamily are critical regulators of germ cell development that act as extracellular ligands of the signal transduction pathways regulating proliferation, apoptosis and other aspects of cell behaviour. As a member of the TGF-β superfamily, growth differentiation factor 9 (GDF9) plays a critical role in ovarian follicular development and the ovulation rate in females; however, its role in the testis has not been well elucidated. The aim of this study was to investigate the expression of GDF9 and its receptor genes BMPRII and ALK5 in prepuberal bovine Sertoli cells (SCs)...
March 23, 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/28329136/chronic-resveratrol-treatment-inhibits-mrc5-fibroblast-sasp-related-protumoral-effects-on-melanoma-cells
#5
Beatrice Menicacci, Anna Laurenzana, Anastasia Chillà, Francesca Margheri, Silvia Peppicelli, Elisabetta Tanganelli, Gabriella Fibbi, Lisa Giovannelli, Mario Del Rosso, Alessandra Mocali
Cellular senescence is related to organismal aging and is observed after DNA damaging cancer therapies, that induce tumor-suppressive modifications, but it is characterized by a strong increase in secreted factors, termed the "senescence-associated secretory phenotype" (SASP). Particularly, SASP from stroma senescent fibroblasts creates a cancer-favoring microenvironment, providing targets for anti-cancer interventions. In the present article, chronic treatment (5 weeks) with 5 µM resveratrol has been used to modulate senescence-related protumoral features of MRC5 fibroblasts, reducing SASP-related interleukins IL1α, IL1β, IL6, and IL8; transforming-growth-factor-β (TGFβ); matrix metallo-proteinases MMP3 and MMP2; urokinase plasminogen activator (uPA); receptor proteins uPAR, IL6R, insulin growth factor receptor-1 (IGF-1R), TGFβ-R2, and CXCR4...
January 20, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28324051/androgen-stimulates-growth-of-mouse-preantral-follicles-in-vitro-interaction-with-follicle-stimulating-hormone-and-with-growth-factors-of-the-tgf%C3%AE-superfamily
#6
Mhairi Laird, Kacie Thomson, Mark Fenwick, Jocelyn Mora, Stephen Franks, Kate Hardy
Androgens are essential for the normal function of mature antral follicles but also have a role in the early stages of follicle development. Polycystic ovary syndrome (PCOS), the commonest cause of anovulatory infertility, is characterized by androgen excess and aberrant follicle development that includes accelerated early follicle growth. We have examined the effects of testosterone and dihydrotestosterone (DHT) on development of isolated mouse preantral follicles in culture with the specific aims of investigating interaction with FSH, the steroidogenic pathway and with growth factors of the TGFβ superfamily that are known to have a role in early follicle development...
January 24, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324043/reduced-transforming-growth-factor-beta-activity-in-the-endometrium-of-women-with-heavy-menstrual-bleeding
#7
J A Maybin, L Boswell, V J Young, W C Duncan, Hod Critchley
Context: Heavy menstrual bleeding (HMB) is common and incapacitating. Aberrant menstrual endometrial repair may result in HMB. The TGFβ superfamily contributes to tissue repair, but its role in HMB is unknown. Objective: We hypothesised that TGFβ1 is important for endometrial repair and women with HMB have aberrant TGFβ1 activity at menses. Participants/Setting: Endometrial biopsies were collected from women and menstrual blood loss objectively measured (HMB >80ml/cycle, normal menstrual bleeding, NMB <80ml)...
January 3, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28324007/aberrant-tgf-%C3%AE-signaling-drives-castration-resistant-prostate-cancer-in-a-male-mouse-model-of-prostate-tumorigenesis
#8
Hong Pu, Diane Begemann, Natasha Kyprianou
The androgen receptor (AR) plays a critical role as a driver of castration-resistant-prostate cancer (CRPC). Our previous studies demonstrated that disruption of transforming growth factor-β (TGF-β) signaling via introduction of dominant-negative TGF-β type II receptor (DNTGF-RβII) in the prostate epithelium of transgenic adenocarcinoma of the prostate (TRAMP) mice accelerated tumor. This study investigated the consequences of disrupted TGF-β signaling on prostate tumor growth under conditions of castration-induced androgen deprivation (ADT) in the pre-clinical model DNTGFβRII...
March 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28321644/vinpocetine-attenuates-pathological-cardiac-remodeling-by-inhibiting-cardiac-hypertrophy-and-fibrosis
#9
Mei-Ping Wu, Yi-Shuai Zhang, Xiangbin Xu, Qian Zhou, Jian-Dong Li, Chen Yan
PURPOSE: Pathological cardiac remodeling, characterized by cardiac hypertrophy and fibrosis, is a pathological feature of many cardiac disorders that leads to heart failure and cardiac arrest. Vinpocetine, a derivative of the alkaloid vincamine, has been used for enhancing cerebral blood flow to treat cognitive impairment. However, its role in pathological cardiac remodeling remains unknown. The aim of this study is to examine the effect of vinpocetine on pathological cardiac remodeling induced by chronic stimulation with angiotensin II (Ang II)...
March 20, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28321218/the-induction-and-maintenance-of-transplant-tolerance-engages-both-regulatory-and-anergic-cd4-t-cells
#10
Alix Besançon, Marije Baas, Tania Goncalves, Fabrice Valette, Herman Waldmann, Lucienne Chatenoud, Sylvaine You
Therapeutic tolerance to self-antigens or foreign antigens is thought to depend on constant vigilance by Foxp3(+) regulatory T cells (Tregs). Previous work using a pancreatic islet allograft model and a short pulse of CD3 antibody therapy has shown that CD8(+) T cells become anergic and use TGFβ and coinhibitory signaling as their contribution to the tolerance process. Here, we examine the role of CD4(+) T cells in tolerization by CD3 antibodies. We show that both Foxp3(+) Tregs and CD4(+) T cell anergy play a role in the induction of tolerance and its maintenance...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28315837/a-search-for-genes-mediating-the-growth-promoting-function-of-tgf%C3%AE-in-the-drosophila-melanogaster-wing-disc
#11
Covadonga F Hevia, Ana López-Varea, Nuria Esteban, Jose F de Celis
TGFβ signalling has a complex influence in cell proliferation, acting to stop cell division in differentiating cells, but also promoting cell division in immature cells. The activity of the pathway in Drosophila is mostly required to stimulate the proliferation of neural and epithelial tissues. Most interestingly, this function is not absolutely required for cell division, but it is needed for these tissues to reach their correct size. It is not known how TGFβ signalling promotes cell division in imaginal discs, or what are the interactions between TGFβ activity and other signalling pathways regulating cell proliferation...
March 17, 2017: Genetics
https://www.readbyqxmd.com/read/28314381/dysregulation-of-alveolar-macrophage-ppar%C3%AE-nadph-oxidases-and-tgf%C3%AE-sub-1-sub-in-otherwise-healthy-hiv-infected-individuals
#12
Samantha M Yeligar, Janine M Ward, Frank L Harris, Lou Ann Brown, David Guidot, Sushma K Cribbs
<u>Rationale:</u> Despite antiretroviral therapy (ART), respiratory infections increase mortality in individuals living with chronic human immunodeficiency virus (HIV) infection. In experimental and clinical studies of chronic HIV infection, alveolar macrophages (AMs) exhibit impaired phagocytosis and bacterial clearance. Peroxisome proliferator-activated receptor (PPAR)γ, NADPH oxidase (Nox) isoforms Nox1, Nox2, Nox4, and transforming growth factor-beta 1 (TGFβ<sub>1</sub>) are critical mediators of AM oxidative stress and phagocytic dysfunction...
March 17, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28314256/hydrogen-peroxide-enhances-tgf%C3%AE-mediated-epithelial-to-mesenchymal-transition-in-human-mammary-epithelial-mcf-10a-cells
#13
Daisuke Iizuka, Megumi Sasatani, Mary Helen Barcellos-Hoff, Kenji Kamiya
AIM: This study investigated the effect of reactive oxygen species (ROS) on transforming growth factor (TGF)-β-mediated epithelial-to-mesenchymal transition (EMT) in order to clarify the influence of ROS and TGFβ on the induction of dysplasia and ultimately, tumorigenesis. MATERIALS AND METHODS: Confluent MCF-10A human mammary epithelial cells were treated with H2O2 for 1 h, then reseeded at low density in the presence of TGFβ and cultured until confluence. RESULTS: Hydrogen peroxide (H2O2, 250 μM) enhanced TGFβ-mediated EMT, as evidenced by increased expression of EMT-associated transcription factors, which was accompanied by increased nuclear localization of phosphorylated SMAD family member 2 (SMAD2) and up-regulation of the TGFβ signaling pathway components mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28314112/can-mesenchymal-stem-cells-pretreated-with-platelet-rich-plasma-modulate-tissue-remodeling-in-a-rat-burn
#14
Hanan Hosni, Laila A Rashed, Soheir Mahfouz, Rania Elsayed Hussein, Marwa Alkaffas, Shaimaa Mostafa, Azza Abusree
AIM: To study the effect of PRP on BM-MSCs proliferation and to investigate their role on healing of experimental burn injury and possible mechanism of action. METHOD: Our work divided into in vitro and in vivo studies. In vitro study included,: MSCs and MSCs treated with PRP. TGF-β level and cell proliferation were assesed. In vivo study, 72 rats divided equally into 6 groups: control, burn, burn with MSCs, burn with PRP, burn with both MSCs and PRP and burn with MSCs pretreated with PRP...
March 17, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28304388/pirfenidone-inhibits-post-traumatic-proliferative-vitreoretinopathy
#15
B N M K Khanum, R Guha, V P Sur, S Nandi, S K Basak, A Konar, S Hazra
PurposeThe purpose of the study was to evaluate the efficacy and safety of intravitreal pirfenidone for inhibition of proliferative vitreoretinopathy (PVR) in a model of penetrating ocular injury.Patients and methodsPenetrating trauma was induced on the retina of rabbit and treated either with 0.1 ml of phosphate-buffered saline (PBS) or 0.1 ml of 0.5% pirfenidone, and development of PVR was evaluated clinically and graded after 1 month. Histopathology and immunohistochemistry with transforming growth factor beta (TGFβ), alpha smooth muscle actin (αSMA), and collagen-1 were performed to assess the fibrotic changes...
March 17, 2017: Eye
https://www.readbyqxmd.com/read/28303407/evodiamine-attenuates-tgf-%C3%AE-1-induced-fibroblast-activation-and-endothelial-to-mesenchymal-transition
#16
Qing-Qing Wu, Yang Xiao, Xiao-Han Jiang, Yuan Yuan, Zheng Yang, Wei Chang, Zhou-Yan Bian, Qi-Zhu Tang
The aim of this study is to investigate the effect of evodiamine on fibroblast activation in cardiac fibroblasts and endothelial to mesenchymal transition (EndMT) in human umbilical vein endothelial cells (HUVECs). Neonatal rat cardiac fibroblasts were stimulated with transforming growth factor beta 1 (TGF-β1) to induce fibroblast activation. After co-cultured with evodiamine (5, 10 μM), the proliferation and pro-fibrotic proteins expression of cardiac fibroblasts were evaluated. HUVECs were also stimulated with TGF-β1 to induce EndMT and treated with evodiamine (5, 10 μM) at the same time...
March 16, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28302753/erythropoietin-receptor-mediated-molecular-crosstalk-promotes-t-cell-immunoregulation-and-transplant-survival
#17
Carolina Purroy, Robert L Fairchild, Toshiaki Tanaka, William M Baldwin, Joaquin Manrique, Joren C Madsen, Robert B Colvin, Alessandro Alessandrini, Bruce R Blazar, Miguel Fribourg, Chiara Donadei, Umberto Maggiore, Peter S Heeger, Paolo Cravedi
Although spontaneous kidney transplant acceptance/tolerance occurs in mice and occasionally in humans, mechanisms remain unclear. Herein we test the hypothesis that EPO, a hormone predominantly produced by the adult kidney, has immunomodulating properties that are required for spontaneous kidney graft acceptance. In vitro, in a manner dependent on the EPO receptor and CD131 on antigen-presenting cells, EPO induced the secretion of active TGFβ by antigen-presenting cells, which in turn converted naïve CD4(+) T cells into functional Foxp3(+) regulatory T cells (Treg)...
March 16, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28302086/extracellular-hsp90-and-tgf%C3%AE-regulate-adhesion-migration-and-anchorage-independent-growth-in-a-paired-colon-cancer-cell-line-model
#18
Jo-Anne de la Mare, Tamarin Jurgens, Adrienne L Edkins
BACKGROUND: Tumour metastasis remains the major cause of death in cancer patients and, to date, the mechanism and signalling pathways governing this process are not completely understood. The TGF-β pathway is the most commonly mutated pathway in cancer, however its role in cancer progression is controversial as it can function as both a promoter and a suppressor of metastasis. Although previous studies have suggested a role for the molecular chaperone Hsp90 in regulating the TGF-β pathway, the level at which this occurs as well as the consequences in terms of colon cancer metastasis are unknown...
March 16, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28301874/veph1-expression-decreases-vascularisation-in-ovarian-cancer-xenografts-and-inhibits-vegfa-and-il8-expression-through-inhibition-of-akt-activation
#19
Premalatha Shathasivam, Alexandra Kollara, Thomasina Spybey, Soyeon Park, Blaise Clarke, Maurice J Ringuette, Theodore J Brown
BACKGROUND: VEPH1 is amplified in several cancers including ovarian but its impact on tumour progression is unknown. Previous work has shown that VEPH1 inhibits TGFβ signalling while its Drosophila ortholog increases tissue growth, raising the possibility that VEPH1 could impact tumour growth or progression. METHODS: A CRISPR approach was used to disrupt VEPH1 expression in ovarian cancer ES-2 cells, while VEPH1-negative SKOV3 cells were stably transfected with VEPH1 cDNA...
March 16, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28301516/follistatin-attenuates-radiation-induced-fibrosis-in-a-murine-model
#20
Helen B Forrester, David M de Kretser, Trevor Leong, Jim Hagekyriakou, Carl N Sprung
PURPOSE: Fibrosis can be a disabling, severe side effect of radiotherapy that can occur in patients, and for which there is currently no effective treatment. The activins, proteins which are members of the TGFβ superfamily, have a major role in stimulating the inflammatory response and subsequent fibrosis. Follistatin is an endogenous protein that binds the activins virtually irreversibly and inhibits their actions. These studies test if follistatin can attenuate the fibrotic response using a murine model of radiation-induced fibrosis...
2017: PloS One
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