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Barbara Jung, Jonas J Staudacher, Daniel Beauchamp
Transforming growth factor beta (TGFB) cytokines signal via a complex network of pathways to regulate proliferation, differentiation, adhesion, migration, and other functions in many cell types. A high percentage of colorectal tumors contain mutations that disrupt TGFB family member signaling. We review how TGFB family member signaling is altered during development of colorectal cancer, models of study, interaction of pathways, and potential therapeutic strategies.
October 20, 2016: Gastroenterology
Eliza Tsitoura, Athol U Wells, Kostantinos Karagiannis, Ismini Lasithiotaki, Eirini Vasarmidi, Eleni Bibaki, Chara Koutoulaki, Hiroe Sato, Demetrios A Spandidos, Nikolaos M Siafakas, George Sourvinos, Katerina M Antoniou
MicroRNA signatures of BAL cells and alveolar macrophages are currently lacking in IPF. Here we sought to investigate the expression of fibrosis-related microRNAs in the cellular component of the BAL in IPF. We thus focused on microRNAs previously associated with fibrosis (miR-29a, miR-29b, miR-29c, let-7d, and miR-21) and rapid IPF progression (miR-185, miR-210, miR-302c-3p miR-376c and miR-423-5p). Among the tested microRNAs miR-29a and miR-185 were found significantly downregulated in IPF while miR-302c-3p and miR-376c were not expressed by BAL cells...
October 18, 2016: Oncotarget
Fang Zhang, Catherine Sodroski, Helen Cha, Qisheng Li, T Jake Liang
BACKGROUND & AIMS: The signaling molecule and transcriptional regulator SMAD6, which inhibits the transforming growth factor beta (TGFB) signaling pathway, is required for infection of hepatocytes by hepatitis C virus (HCV). We investigated the mechanisms by which SMAD6, and another inhibitory SMAD (SMAD7), promote HCV infection in human hepatoma cells and hepatocytes. METHODS: We infected Huh7 and Huh7.5.1 cells and primary human hepatocytes with JFH1 HCVcc; we measured HCV binding, intracellular levels of HCV RNA, and expression of target genes...
September 29, 2016: Gastroenterology
Xin Fang, Yang Gao, Qinglei Li
Ovarian granulosa cell tumors (GCTs) are rare gynecologic tumors in women. Due to the rarity and limited research efforts invested, the etiology of GCTs remains poorly defined. A landmark study has discovered the mutation of forkhead box L2 (FOXL2) as a genetic hallmark of adult GCTs in the human. However, our understanding of the role of cell signaling in GCT development is far from complete. Increasing lines of evidence highlight the importance of TGF-beta (TGFB) superfamily signaling in the pathogenesis of GCTs...
September 28, 2016: Biology of Reproduction
Takayuki Kawai, Kentaro Yasuchika, Satoru Seo, Tatsuya Higashi, Takamichi Ishii, Yuya Miyauchi, Hidenobu Kojima, Ryoya Yamaoka, Hokahiro Katayama, Elena Yukie Yoshitoshi, Satoshi Ogiso, Sadahiko Kita, Katsutaro Yasuda, Ken Fukumitsu, Yuji Nakamoto, Etsuro Hatano, Shinji Uemoto
Purpose The current lack of tools for easy assessment of cancer stem cells (CSCs) prevents the development of therapeutic strategies for hepatocellular carcinoma (HCC). We previously reported that keratin 19 (K19) is a novel HCC-CSC marker, and that positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) is an effective method for predicting postoperative outcome in HCC. Herein, we examined whether K19+ HCC-CSCs can be tracked using 18F-FDG-PET. Experimental Design K19 and glucose transporter-1 (GLUT1) expression was evaluated by immunohistochemistry in 98 HCC patients who underwent 18F-FDG-PET scans before primary tumor resection...
September 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Bridget Wiafe, Adetola Adesida, Thomas Churchill, Esther Ekpe Adewuyi, Zack Li, Peter Metcalfe
Partial bladder outlet obstruction (pBOO) is characterized by exaggerated stretch, hydrodynamic pressure, and inflammation which cause significant damage and fibrosis to the bladder wall. Several studies have implicated hypoxia in its pathophysiology. However, the isolated progressive effects of hypoxia on bladder cells are not yet defined. Sub-confluent normal human bladder smooth muscle cells (hbSMC) were cultured in 3% O2 tension for 2, 24, 48, and 72 h. RNA, cellular proteins, and secreted proteins were used for gene expression analysis, immunoblotting, and ELISA, respectively...
September 8, 2016: In Vitro Cellular & Developmental Biology. Animal
Syn Kok Yeo, Jun-Lin Guan
Intra-tumor heterogeneity can be attributed in part to the ability of tumor cells to acquire traits associated with less differentiated cells. In MMTV-PyMT mammary tumors, this hierarchical heterogeneity can be illustrated with the use of ITGB1/CD29(hi) ITGB3/CD61(+) markers to enrich for mammary stem-like cells and ALDH(+) to identify luminal progenitor-like cells. Macroautophagy/autophagy appears to be important for maintaining the cancer stem-like traits of both these populations. Interestingly, the regulation of these distinct cancer stem-like cells by autophagy occurs through EGFR-STAT3 and TGFB/TGF-β-SMAD pathways, respectively...
October 2, 2016: Autophagy
David J Sharkey, Kelton P Tremellen, Nancy E Briggs, Gustaaf A Dekker, Sarah A Robertson
STUDY QUESTION: Do seminal plasma transforming growth factor-β (TGFB) cytokines vary within individuals over time, and does this relate to sperm parameters, age or prior abstinence? SUMMARY ANSWER: Activin A and follistatin, and to a lesser extent TGFB1, TGFB2 and TGFB3, vary within individuals over time, in association with duration of abstinence. WHAT IS ALREADY KNOWN: Seminal plasma TGFB cytokines can influence sperm function and reproductive success through interactions with the female reproductive tract after coitus...
October 2016: Human Reproduction
Belinda J Thomas, Keiko Kan-O, Kate Loveland, Jack A Elias, Philip G Bardin
Transforming growth factor beta (TGFB) regulates cell proliferation, differentiation, apoptosis and matrix homeostasis and is intimately involved in fibrosis. TGFB expression is increased in fibrotic lung diseases such as idiopathic pulmonary fibrosis (IPF) but also in chronic inflammatory conditions such as chronic obstructive pulmonary disease (COPD) and asthma. In addition to profibrotic activities, the molecule also exhibits profound immune-suppressive actions involving both innate and adaptive responses, but this aspect of TGFB biology is often overlooked...
September 7, 2016: American Journal of Respiratory Cell and Molecular Biology
Shigeo Otake, Min Kyun Park
Gonadal sex differentiation proceeds by interplay of various genes including the transcription factors and secretory factors in a complex network. The sex-differentiating genes are expressed not only during early sex differentiation but also throughout the gonadal development, and even in the adult gonads. In addition, the evidence that they actually function in the adult gonads have been accumulated from the studies using the conditional knockout mice. However, many previous studies were focused on one single gene though those genes function in a network...
August 31, 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
Norelia Torrealba, Gonzalo Rodríguez-Berriguete, Benito Fraile, Gabriel Olmedilla, Pilar Martínez-Onsurbe, Manuel Guil-Cid, Ricardo Paniagua, Mar Royuela
BACKGROUND: This work is focused on finding new markers that complement or diagnoses currently used towards improving knowledge histological and statistical aspects that allow us to predict the local stage carcinomas and to identify and understand all the factors related to the progression of this disease. MATERIALS AND METHODS: Prostates were obtained from: normal prostates from 20 men, diagnosis of BPH (Benign Prostatic Hyperplasia) from 35 men and prostate cancer from 86 men...
August 12, 2016: Cytokine
Nienke Grotenhuis, Samantha F H De Witte, Gerjo J V M van Osch, Yves Bayon, Johan F Lange, Yvonne M Bastiaansen-Jenniskens
BACKGROUND: Macrophages and mesenchymal stem cells (MSCs) are important cells in wound healing. We hypothesized that the cross-talk between macrophages and adipose tissue-derived MSCs (ASCs) is biomaterial dependent, thereby influencing processes involved in wound healing. MATERIALS AND METHODS: The effect of macrophages cultured on polypropylene (PP) or polyethylene terephthalate coated with a collagen film (PET/Col) on ASCs in monolayer or on the same material was examined either through conditioned medium (CM) or in a direct coculture...
September 2016: Tissue Engineering. Part A
A V Elchaninov, T Kh Fatkhudinov, N Yu Usman, I V Arutyunyan, A V Makarov, E Yu Kananykhina, V V Glinkina, G B Bolshakova, G T Sukhikh
Expression of il1b, il6, il10, tnfa, hgf, tgfb, vegf, and fgf2 genes in the lungs and kidneys was examined on rat model of liver regeneration after subtotal hepatectomy. Enhanced expression of il6, il10, tnfa, hgf, and fgf2 genes was detected at the early terms after 80% liver resection.
July 2016: Bulletin of Experimental Biology and Medicine
Judy G Johnson, Jacob P Bray, William H Risher, Alan David Kaye
Loeys-Dietz syndrome (LDS) is a rare autosomal dominant disease related to genetic mutations in receptors for the cytokine transforming growth factor-receptor type 1 (TGFB-R1) or 2 gene (TGFB-R2) on the cell surface. LDS results in abnormal protein synthesis and dysfunctional connective tissue, which can result in unique cardiovascular anesthesia challenges related to perioperative management. Patients with LDS may manifest hypertelorism, bifid uvula or cleft palate, and arterial tortuosity. Virtually all LDS patients show some type of abnormal skin findings and bleeding tendency...
June 2016: Middle East Journal of Anesthesiology
Takayuki Kawai, Kentaro Yasuchika, Takamichi Ishii, Yuya Miyauchi, Hidenobu Kojima, Ryoya Yamaoka, Hokahiro Katayama, Elena Yukie Yoshitoshi, Satoshi Ogiso, Sadahiko Kita, Katsutaro Yasuda, Ken Fukumitsu, Junji Komori, Etsuro Hatano, Yoshiya Kawaguchi, Shinji Uemoto
The current lack of cancer stem cell (CSC) markers that are easily evaluated by blood samples prevents the establishment of new therapeutic strategies in hepatocellular carcinoma (HCC). Herein, we examined whether sex determining region Y-box 9 (SOX9) represents a new CSC marker, and whether osteopontin (OPN) can be used as a surrogate marker of SOX9 in HCC. In HCC cell lines transfected with a SOX9 promoter-driven enhanced green fluorescence protein gene, FACS-isolated SOX9(+) cells were capable of self-renewal and differentiation into SOX9(-) cells, and displayed high proliferation capacity in vitro...
2016: Scientific Reports
Héctor Cordero, Manuela Mauro, Alberto Cuesta, Matteo Cammarata, María Ángeles Esteban
Skin is the first barrier of defense on fish, which is crucial to protection against different stressors, including pathogens. Skin samples obtained from dorsal and ventral part of Sparus aurata specimens were incubated with Photobacterium damselae subsp. piscicida (a pathogen for this fish species), with Shewanella putrefaciens Pdp11 (a probiotic bacteria isolated from healthy gilthead seabream skin) or with both bacteria. The gene expression profile of nine cytokines (il1b, tnfa, il6, il7, il8, il15, il18, il10 and tgfb) was studied by qPCR in all the skin samples...
September 2016: Fish & Shellfish Immunology
Olivier Monestier, Véronique Blanquet
The WFIKKN (WAP, Follistatin/kazal, Immunoglobulin, Kunitz and Netrin domain-containing) protein family is composed of two multidomain proteins: WFIKKN1 and WFIKKN2. They were formed by domain shuffling and are likely present in deuterostoms. The WFIKKN (also called GASP) proteins are well known for their function in muscle and skeletal tissues, namely, inhibition of certain members of the transforming growth factor beta (TGFB) superfamily such as myostatin (MSTN) and growth and differentiation factor 11 (GDF11)...
June 11, 2016: Cytokine & Growth Factor Reviews
T F Schilling, J Sosnik, Q Nie
Morphogens were originally defined as secreted signaling molecules that diffuse from local sources to form concentration gradients, which specify multiple cell fates. More recently morphogen gradients have been shown to incorporate a range of mechanisms including short-range signal activation, transcriptional/translational feedback, and temporal windows of target gene induction. Many critical cell-cell signals implicated in both embryonic development and disease, such as Wnt, fibroblast growth factor (Fgf), hedgehog (Hh), transforming growth factor beta (TGFb), and retinoic acid (RA), are thought to act as morphogens, but key information on signal propagation and ligand distribution has been lacking for most...
2016: Methods in Cell Biology
Tyler D Brown, Tiago S Hori, Xi Xue, Chang Lin Ye, Derek M Anderson, Matthew L Rise
The inclusion of plant meals in diets of farmed Atlantic salmon can elicit inflammatory responses in the distal intestine (DI). For the present work, fish were fed a standard fish meal (FM) diet or a diet with partial replacement of FM with solvent-extracted camelina meal (CM) (8, 16, or 24 % CM inclusion) during a 16-week feeding trial. A significant decrease in growth performance was seen in fish fed all CM inclusion diets (Hixson et al. in Aquacult Nutr 22:615-630, 2016). A 4x44K oligonucleotide microarray experiment was carried out and significance analysis of microarrays (SAM) and rank products (RP) methods were used to identify differentially expressed genes between the DIs of fish fed the 24 % CM diet and those fed the FM diet...
June 2016: Marine Biotechnology
Shikha Shrivastava, Eric G Meissner, Emily Funk, Seerat Poonia, Virender Shokeen, Arun Thakur, Bhawna Poonia, Shiv Kumar Sarin, Nirupma Trehanpati, Shyamasundaran Kottilil
BACKGROUND AND AIMS: HCV GT-3 has a more pronounced effect on hepatic steatosis and host lipids than other HCV genotypes and is proving less responsive to all oral interferon-free treatment with direct acting antiviral agents. As both HCV GT3 infection and NASH can result in steatosis and cirrhosis, we asked whether hepatic transcriptional profiles reflective of the host response to inflammation differed based on the etiology of injury. METHODS: Hepatic gene expression was determined for 48 pre-selected genes known to be associated with hepatic interferon signaling and lipid metabolic pathways in treatment-naïve HCV GT-3 (n = 9) and NASH (n = 14) patients...
May 18, 2016: Hepatology International
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