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https://www.readbyqxmd.com/read/28734833/transforming-growth-factor-beta-promotes-liver-tumorigenesis-in-mice-via-upregulation-of-snail
#1
Hyuk Moon, Hye-Lim Ju, Sook In Chung, Kyung Joo Cho, Jung Woo Eun, Suk Woo Nam, Kwang-Hyub Han, Diego F Calvisi, Simon Weonsang Ro
BACKGROUND & AIMS: Transforming growth factor beta (TGFB) suppresses early stages of tumorigenesis, but also contributes to migration and metastasis of cancer cells. A large number of human tumors contain mutations that inactivate its receptors, or downstream proteins such as Smad transcription factors, indicating that the TGFB signaling pathway prevents tumor growth. We investigated the effects of TGFB inhibition on liver tumorigenesis in mice. METHODS: C57BL/6 mice received hydrodynamic tail injections of transposons encoding HRAS(G12V) and a short hairpin RNA (shRNA) to downregulate p53, or those encoding HRAS(G12V) and MYC, or those encoding HRAS(G12V) and TAZ(S89), to induce liver tumor formation; mice were also given injections of transposons encoding SMAD7 or shRNA against SMAD2, SMAD3, SMAD4, or SNAI1 (Snail), with or without ectopic expression of Snail...
July 19, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28733348/molecular-forms-of-ruminant-bmp15-and-gdf9-and-putative-interactions-with-receptors
#2
Derek A Heath, Janet Pitman, Kenneth P McNatty
Bone morphogenetic factor 15 (BMP15) and growth differentiation factor 9 (GDF9) are oocyte-secreted factors with demonstrable effects on ovarian follicular development and ovulation-rate. However, the molecular forms of BMP15 and GDF9 produced by oocytes remains unclear. The aims herein, using Western blotting (WB) procedures with specific monoclonal antibodies (mabs), were to identify the molecular forms of BMP15 and GDF9 synthesised and secreted by isolated ovine (o) and bovine (b) oocytes in vitro. The mabs were known to recognise the biological forms of BMP15 or GDF9 since they had previously been shown to inhibit their bioactivities in vitro and in vivo...
July 21, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28679671/breast-regression-protein-39-chitinase-3-like-1-promotes-renal-fibrosis-after-kidney-injury-via-activation-of-myofibroblasts
#3
Tinika A Montgomery, Leyuan Xu, Sherene Mason, Amirtha Chinnadurai, Chun Geun Lee, Jack A Elias, Lloyd G Cantley
The normal response to kidney injury includes a robust inflammatory infiltrate of PMNs and macrophages. We previously showed that the small secreted protein breast regression protein-39 (BRP-39), also known as chitinase 3-like 1 (CHI3L1) and encoded by the Chi3l1 gene, is expressed at high levels by macrophages during the early stages of kidney repair and promotes tubular cell survival via IL-13 receptor α2 (IL13Rα2)-mediated signaling. Here, we investigated the role of BRP-39 in profibrotic responses after AKI...
July 5, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28665611/comprehensive-myocardial-proteogenomics-profiling-reveals-c-ebp%C3%AE-as-the-key-factor-in-the-lipid-storage-of-arvc
#4
Liang Chen, Fan Yang, Xiao Chen, Man Rao, Ning-Ning Zhang, Kai Chen, HaiTeng Deng, Jiang-Ping Song, Sheng-Shou Hu
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is hereditary cardiomyopathy characterized by the fibro-fatty replacement of the myocardium. A small number of noncomprehensive profiling studies based on human cardiac tissues have been conducted and reported; consequently, ARVC's gene expression pattern characteristics remain largely undocumented. Our study applies large-scaled, quantitative proteomics based on TMT-labeled LC-MS/MS to analyze the left and right ventricular myocardium of four ARVC and four DCM explanted hearts to compare them with normal hearts...
July 13, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28662367/inhibition-of-the-mir-17-92-cluster-separates-stages-of-palatogenesis
#5
R J Ries, W Yu, N Holton, H Cao, B A Amendt
The role that noncoding regions of the genome play in the etiology of cleft palate is not well studied. A novel method of microRNA (miR) inhibition that allows for specific miR knockdown in vivo has been developed by our laboratory. To further understand the role of miRs in palatogenesis, we used a new mouse model to inhibit specific miRs within the miR-17-92 cluster. Transgenic mice expressing inhibitory complexes for miR-17 and miR-18 manifested a clefting phenotype that was distinct from that observed in mice carrying inhibitory complexes for miR-17, miR-18, miR-19, and miR-92...
June 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28659758/chronic-oxidative-stress-mitochondrial-dysfunction-nrf2-activation-and-inflammation-in-the-hippocampus-accompany-heightened-systemic-inflammation-and-oxidative-stress-in-an-animal-model-of-gulf-war-illness
#6
Geetha A Shetty, Bharathi Hattiangady, Dinesh Upadhya, Adrian Bates, Sahithi Attaluri, Bing Shuai, Maheedhar Kodali, Ashok K Shetty
Memory and mood dysfunction are the key symptoms of Gulf war illness (GWI), a lingering multi-symptom ailment afflicting >200,000 veterans who served in the Persian Gulf War-1. Research probing the source of the disease has demonstrated that concomitant exposures to anti-nerve gas agent pyridostigmine bromide (PB), pesticides, and war-related stress are among the chief causes of GWI. Indeed, exposures to GWI-related chemicals (GWIR-Cs) and mild stress in animal models cause memory and mood impairments alongside reduced neurogenesis and chronic low-level inflammation in the hippocampus...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28657664/conditional-abrogation-of-transforming-growth-factor-%C3%AE-receptor-1-in-pten-inactivated-endometrium-promotes-endometrial-cancer-progression-in-mice
#7
Yang Gao, Pengfei Lin, John P Lydon, Qinglei Li
Although a putative role for transforming growth factor-β (TGFB) signalling in the pathogenesis of human endometrial cancer has long been proposed, the precise function of TGFB signalling in the development and progression of endometrial cancer remains elusive. Depletion of phosphatase and tensin homologue (PTEN) in the mouse uterus causes endometrial cancer. To identify the potential role of TGFB signalling in endometrial cancer, we simultaneously deleted TGFB receptor 1 (Tgfbr1) and Pten in the mouse uterus by using Cre-recombinase driven by the progesterone receptor (termed Pten(d/d) ;Tgfbr1(d/d) )...
June 28, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28624577/identification-of-an-immune-specific-class-of-hepatocellular-carcinoma-based-on-molecular-features
#8
Daniela Sia, Yang Jiao, Iris Martinez-Quetglas, Olga Kuchuk, Carlos Villacorta-Martin, Manuel Castro de Moura, Juan Putra, Genis Camprecios, Laia Bassaganyas, Nicholas Akers, Bojan Losic, Samuel Waxman, Swan N Thung, Vincenzo Mazzaferro, Manel Esteller, Scott L Friedman, Myron Schwartz, Augusto Villanueva, Josep M Llovet
BACKGROUND & AIMS: Agents that induce an immune response against tumors by altering T-cell regulation have increased survival times of patients with advanced-stage tumors, such as melanoma or lung cancer. We aimed to characterize molecular features of immune cells that infiltrate hepatocellular carcinomas (HCCs) to determine whether these types of agents might be effective against liver tumors. METHODS: We analyzed HCC samples from 956 patients. We separated gene expression profiles from tumor, stromal, and immune cells using a non-negative matrix factorization algorithm...
June 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28613983/azithromycin-attenuates-myofibroblast-differentiation-and-lung-fibrosis-development-through-proteasomal-degradation-of-nox4
#9
Kazuya Tsubouchi, Jun Araya, Shunsuke Minagawa, Hiromichi Hara, Akihiro Ichikawa, Nayuta Saito, Tsukasa Kadota, Nahoko Sato, Masahiro Yoshida, Yusuke Kurita, Kenji Kobayashi, Saburo Ito, Yu Fujita, Hirofumi Utsumi, Haruhiko Yanagisawa, Mitsuo Hashimoto, Hiroshi Wakui, Yutaka Yoshii, Takeo Ishikawa, Takanori Numata, Yumi Kaneko, Hisatoshi Asano, Makoto Yamashita, Makoto Odaka, Toshiaki Morikawa, Katsutoshi Nakayama, Yoichi Nakanishi, Kazuyoshi Kuwano
Accumulation of profibrotic myofibroblasts is involved in the process of fibrosis development during idiopathic pulmonary fibrosis (IPF) pathogenesis. TGFB (transforming growth factor β) is one of the major profibrotic cytokines for myofibroblast differentiation and NOX4 (NADPH oxidase 4) has an essential role in TGFB-mediated cell signaling. Azithromycin (AZM), a second-generation antibacterial macrolide, has a pleiotropic effect on cellular processes including proteostasis. Hence, we hypothesized that AZM may regulate NOX4 levels by modulating proteostasis machineries, resulting in inhibition of TGFB-associated lung fibrosis development...
June 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28536871/impact-of-early-subcultures-on-stemness-migration-and-angiogenic-potential-of-adipose-tissue-derived-stem-cells-and-their-resistance-to-in-vitro-ischemic-condition
#10
Hossein Faghih, Arash Javeri, Masoumeh Fakhr Taha
Adipose tissue-derived stem cells (ADSCs) are capable of multipotential differentiation and express several angiogenic, anti-apoptotic and immunomodulatory markers. These features make adipose tissue as a promising source of stem cells for regenerative medicine. However, for efficient translational use, culture-induced changes in the gene expression profile and resistance of the ADSCs to ischemic environment should be taken into consideration. We compared the expression of some clinically important markers between the unpassaged and third-passaged ADSCs by RT-PCR, qPCR and flow cytometry...
May 23, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28506076/nos2-as-an-emergent-player-in-progression-of-cancer
#11
Douglas D Thomas, David A Wink
Although the inducible form of nitric oxide synthase (NOS2) was initially shown to be a major player as an antitumor component of the immune response, more recent data have shown that NOS2 expression in cancer cells often predicts poor outcome. Unlike growth factors associated with a single oncogenic pathway, nitric oxide (NO) has a ubiquitous nature wherein it simultaneously mediates major oncogenic pathways from Akt/PI3K and RAS/ERK to HIF1a and TGFb. These interactive loops perpetuate oncogenic mechanism that leads to increased cancer stemness, proliferation metastasis, chemoresistance, angiogenesis, and immunosuppression...
June 10, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28500669/anti-m%C3%A3-llerian-hormone-signaling-is-influenced-by-follistatin-288-but-not-14-other-transforming-growth-factor-beta-superfamily-regulators
#12
Yui Kawagishi, Michael W Pankhurst, Yoshio Nakatani, Ian S McLennan
The hypothesis that, in contrast to other transforming growth factor-beta (TGFβ) superfamily ligands, the dose-response curve of Anti-Müllerian hormone (AMH) is unmodulated was tested by examining whether known TGFB superfamily modulators affect AMH signaling, using a P19/BRE luciferase reporter assay. AMHC and AMHN,C activated the reporter with an EC50 of approximately 0.5 nM. Follistatins (FS) produced concentration-dependent increases in AMHC - and AMHN,C -initiated reporter activity, with FS288 being more potent than FS315; however, the maximum bioactivity of AMH was not altered by either follistatin...
July 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28470822/pericyte-derived-bone-morphogenetic-protein-4-underlies-white-matter-damage-after-chronic-hypoperfusion
#13
Maiko T Uemura, Masafumi Ihara, Takakuni Maki, Takayuki Nakagomi, Seiji Kaji, Kengo Uemura, Tomohiro Matsuyama, Raj N Kalaria, Ayae Kinoshita, Ryosuke Takahashi
Subcortical small vessel disease (SVD) is characterized by white matter damage resulting from arteriolosclerosis and chronic hypoperfusion. Transforming growth factor beta 1 (TGFB1) is dysregulated in the hereditary SVD, CARASIL (cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy). However, very little is known about the role of the largest group in the TGFB superfamily - the bone morphogenetic proteins (BMPs) - in SVD pathogenesis. The aim of this study was to characterize signaling abnormalities of BMPs in sporadic SVD...
May 4, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28444170/neuronal-activity-tgf%C3%AE-signaling-and-unpredictable-chronic-stress-modulate-transcription-of-gadd45-family-members-and-dna-methylation-in-the-hippocampus
#14
Daniela Grassi, Henriette Franz, Riccardo Vezzali, Patrick Bovio, Stefanie Heidrich, Fariba Dehghanian, Natalia Lagunas, Catherine Belzung, Kerstin Krieglstein, Tanja Vogel
Neuronal activity is altered in several neurological and psychiatric diseases. Upon depolarization not only neurotransmitters are released but also cytokines and other activators of signaling cascades. Unraveling their complex implication in transcriptional control in receiving cells will contribute to understand specific central nervous system (CNS) pathologies and will be of therapeutically interest. In this study we depolarized mature hippocampal neurons in vitro using KCl and revealed increased release not only of brain-derived neurotrophic factor (BDNF) but also of transforming growth factor beta (TGFB)...
April 21, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28418896/nfkb-is-essential-for-activin-induced-colorectal-cancer-migration-via-upregulation-of-pi3k-mdm2-pathway
#15
Arundhati Jana, Nancy L Krett, Grace Guzman, Ahmer Khalid, Ozkan Ozden, Jonas J Staudacher, Jessica Bauer, Seung Hyun Baik, Timothy Carroll, Cemal Yazici, Barbara Jung
Colorectal cancer (CRC) remains a common and deadly cancer due to metastatic disease. Activin and TGFB (TGFβ) signaling are growth suppressive pathways that exert non-canonical pro-metastatic effects late in CRC carcinogenesis. We have recently shown that activin downregulates p21 via ubiquitination and degradation associated with enhanced cellular migration independent of SMADs. To investigate the mechanism of metastatic activin signaling, we examined activated NFkB signaling and activin ligand expression in CRC patient samples and found a strong correlation...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28390866/activation-of-transforming-growth-factor-beta-1-signaling-in-gastric-cancer-associated-fibroblasts-increases-their-motility-via-expression-of-rhomboid-5-homolog-2-and-ability-to-induce-invasiveness-of-gastric-cancer-cells
#16
Takatsugu Ishimoto, Keisuke Miyake, Tannistha Nandi, Masakazu Yashiro, Nobuyuki Onishi, Kie Kyon Huang, Lin Suling Joyce, Ramnarayanan Kalpana, Su Ting Tay, Yuka Suzuki, Byoung Chul Cho, Daisuke Kuroda, Kota Arima, Daisuke Izumi, Masaaki Iwatsuki, Yoshifumi Baba, Eiji Oki, Masayuki Watanabe, Hideyuki Saya, Kosei Hirakawa, Hideo Baba, Patrick Tan
BACKGROUND & AIMS: Fibroblasts that interact with cancer cells are called cancer-associated fibroblasts (CAFs), which promote progression of different tumor types. We investigated the characteristics and functions of CAFs in diffuse-type gastric cancers (DGCs) by analyzing features of their genome and gene expression patterns. METHODS: We isolated CAFs and adjacent non-cancer fibroblasts (NFs) from 110 gastric cancer (GC) tissues from patients who underwent gastrectomy in Japan from 2008 through 2016...
April 5, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28362822/fasciola-hepatica-reinfection-potentiates-a-mixed-th1-th2-th17-treg-response-and-correlates-with-the-clinical-phenotypes-of-anemia
#17
M Adela Valero, Ignacio Perez-Crespo, Carlos Chillón-Marinas, Messaoud Khoubbane, Carla Quesada, Marta Reguera-Gomez, Santiago Mas-Coma, Manuel Fresno, Núria Gironès
BACKGROUND: Fascioliasis is a severe zoonotic disease of worldwide extension caused by liver flukes. In human fascioliasis hyperendemic areas, reinfection and chronicity are the norm and anemia is the main sign. Herein, the profile of the Th1/Th2/Th17/Treg expression levels is analyzed after reinfection, correlating them with their corresponding hematological biomarkers of morbidity. METHODOLOGY/PRINCIPAL FINDINGS: The experimental design reproduces the usual reinfection/chronicity conditions in human fascioliasis endemic areas and included Fasciola hepatica primo-infected Wistar rats (PI) and rats reinfected at 8 weeks (R8), and at 12 weeks (R12), and negative control rats...
2017: PloS One
https://www.readbyqxmd.com/read/28361317/generation-of-gastrointestinal-organoids-from-human-pluripotent-stem-cells
#18
Jorge O Múnera, James M Wells
Over the past several decades, developmental biologists have discovered fundamental mechanisms by which organs form in developing embryos. With this information it is now possible to generate human "organoids" by the stepwise differentiation of human pluripotent stem cells using a process that recapitulates organ development. For the gastrointestinal tract, one of the first key steps is the formation of definitive endoderm and mesoderm, a process that relies on the TGFb molecule Nodal. Endoderm is then patterned along the anterior-posterior axis, with anterior endoderm forming the foregut and posterior endoderm forming the mid and hindgut...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28337864/molecular-basis-of-growth-proliferation-and-differentiation-of-mammalian-follicular-granulosa-cells
#19
REVIEW
W Kranc, J Budna, R Kahan, A Chachuła, A Bryja, S Ciesiółka, S Borys, M P Antosik, D Bukowska, K P Brussow, M Bruska, M Nowicki, M Zabel, B Kempisty
For normal folliculogenesis and oogenesis to occur many intrinsic and extrinsic factors are needed, i.e. positive feedback of hormone secretion and local ovarian-follicular growth factors distribution. During follicle formation, granulosa cells (GCs) change their morphology and physiological properties. The factors needed for GCs to differentiate within each layer are transforming growth factor beta (TGFB) and insulin-like growth factor (IGF), as well as the activation and modification of biochemical pathways involved in folliculogenesis...
January 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28300161/foxo-transcription-factors-protect-against-the-diet-induced-fatty-liver-disease
#20
Xiaoyan Pan, Yang Zhang, Hyeong-Geug Kim, Suthat Liangpunsakul, X Charlie Dong
Forkhead O transcription factors (FOXOs) have been implicated in glucose and lipid homeostasis; however, the role of FOXOs in the development of nonalcoholic fatty liver disease (NAFLD) is not well understood. In this study, we designed experiments to examine the effects of two different diets-very high fat diet (HFD) and moderately high fat plus cholesterol diet (HFC)-on wildtype (WT) and liver-specific Foxo1/3/4 triple knockout mice (LTKO). Both diets induced severe hepatic steatosis in the LTKO mice as compared to WT controls...
March 16, 2017: Scientific Reports
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