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https://www.readbyqxmd.com/read/27922122/identification-of-critical-paralog-groups-with-indispensable-roles-in-the-regulation-of-signaling-flow
#1
Dezso Modos, Johanne Brooks, David Fazekas, Eszter Ari, Tibor Vellai, Peter Csermely, Tamas Korcsmaros, Katalin Lenti
Extensive cross-talk between signaling pathways is required to integrate the myriad of extracellular signal combinations at the cellular level. Gene duplication events may lead to the emergence of novel functions, leaving groups of similar genes - termed paralogs - in the genome. To distinguish critical paralog groups (CPGs) from other paralogs in human signaling networks, we developed a signaling network-based method using cross-talk annotation and tissue-specific signaling flow analysis. 75 CPGs were found with higher degree, betweenness centrality, closeness, and 'bowtieness' when compared to other paralogs or other proteins in the signaling network...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27919341/human-epidermal-stem-cells-role-in-adverse-skin-reactions-and-carcinogenesis-from-radiation
#2
Michèle T Martin, Adeline Vulin, Jolyon H Hendry
In human skin, keratinopoiesis is based on a functional hierarchy among keratinocytes, with rare slow-cycling stem cells responsible for the long-term maintenance of the tissue through their self-renewal potential, and more differentiated daughter progenitor cells actively cycling to permit epidermal renewal and turn-over every month. Skin is a radio-responsive tissue, developing all types of radiation damage and pathologies, including early tissue reactions such as dysplasia and denudation in epidermis, and later fibrosis in the dermis and acanthosis in epidermis, with the TGF-beta 1 pathway as a known master switch...
October 2016: Mutation Research
https://www.readbyqxmd.com/read/27889505/candesartan-ameliorates-arsenic-induced-hypertensive-vascular-remodeling-by-regularizing-angiotensin-ii-and-tgf-beta-signaling-in-rats
#3
Maibam Wanta Khuman, Sankaran Kutty Harikumar, Abdul Sadam, Manickam Kesavan, Vattaparambil Sukumaran Susanth, Subhashree Parida, Karam Pal Singh, Souvendra Nath Sarkar
Arsenic exposure can cause several cardiovascular diseases, including hypertension, atherosclerosis and microvascular disease. Earlier, we reported that arsenic-mediated enhancement of angiotensin II (AngII) signaling can impair vascular physiology. Here, we investigated whether the AT1 receptor (AT1R) blocker candesartan can ameliorate the arsenic-induced hypertensive vascular remodeling in rats and whether the amelioration could relate to attenuation in vascular AngII and TGF-β signaling. Rats were exposed to sodium arsenite (50ppm) through drinking water for 90 consecutive days...
November 23, 2016: Toxicology
https://www.readbyqxmd.com/read/27888159/transmembrane-tnf-alpha-reverse-signaling-leading-to-tgf-beta-production-is-selectively-activated-by-tnf-targeting-molecules-therapeutic-implications
#4
REVIEW
Zsuzsa Szondy, Anna Pallai
Tumor necrosis factor (TNF)-α is a potent pro-inflammatory cytokine exerting pleiotropic effects on various cell types. It is synthesized in a precursor form called transmembrane TNF-α (mTNF-α) which, after being processed by metalloproteinases, is released in a soluble form to mediate its biological activities through Type 1 and 2 TNF receptors in TNF receptor expressing cells. In addition to acting in soluble form, TNF-α also acts in the transmembrane form both as a ligand by activating TNF receptors, as well as a receptor that transmits outside-to-inside (reverse) signals back into mTNF-α bearing cells...
November 22, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27883077/tgf-beta-receptor-ii-interacting-protein-1-an-intracellular-protein-has-an-extracellular-role-as-a-modulator-of-matrix-mineralization
#5
Amsaveni Ramachandran, Sriram Ravindran, Chun-Chieh Huang, Anne George
Transforming growth factor beta receptor II interacting protein 1 (TRIP-1), a predominantly intracellular protein is localized in the ECM of bone. TRIP-1 lacks a signal peptide, therefore, in this study, we provide evidence that intracellular TRIP-1 can be packaged and exported to the ECM via exosomes. Overexpression of TRIP-1 in MC3T3-E1 cells resulted in increased matrix mineralization during differentiation and knockdown resulted in reduced effects. In vivo function of TRIP-1 was studied by an implantation assay performed using TRIP-1 overexpressing and knockdown cells cultured in a 3-dimmensional scaffold...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27880731/smad4-in-t-cells-plays-a-protective-role-in-the-development-of-autoimmune-sj%C3%A3-gren-s-syndrome-in-the-nonobese-diabetic-mouse
#6
Donghee Kim, Jae Young Kim, Hee-Sook Jun
We investigated the role of Smad4, a signaling molecule of the TGF-beta pathway, in T cells on the pathology of Sjögren's syndrome (SS) in nonobese diabetic (NOD) mice, an animal model of SS. T cell-specific Smad4-deleted (Smad4fl/fl,CD4-Cre; Smad4 tKO) NOD mice had accelerated development of SS compared with wild-type (Smad4+/+,CD4-Cre; WT) NOD mice, including increased lymphocyte infiltration into exocrine glands, decreased tear and saliva production, and increased levels of autoantibodies at 12 weeks of age...
November 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27874859/a-single-heterochronic-blood-exchange-reveals-rapid-inhibition-of-multiple-tissues-by-old-blood
#7
Justin Rebo, Melod Mehdipour, Ranveer Gathwala, Keith Causey, Yan Liu, Michael J Conboy, Irina M Conboy
Heterochronic parabiosis rejuvenates the performance of old tissue stem cells at some expense to the young, but whether this is through shared circulation or shared organs is unclear. Here we show that heterochronic blood exchange between young and old mice without sharing other organs, affects tissues within a few days, and leads to different outcomes than heterochronic parabiosis. Investigating muscle, liver and brain hippocampus, in the presence or absence of muscle injury, we find that, in many cases, the inhibitory effects of old blood are more pronounced than the benefits of young, and that peripheral tissue injury compounds the negative effects...
November 22, 2016: Nature Communications
https://www.readbyqxmd.com/read/27814646/blockage-of-hemichannels-alters-gene-expression-in-osteocytes-in-a-high-magneto-gravitational-environment
#8
Huiyun Xu, Dandan Ning, Dezhi Zhao, Yunhe Chen, Dongdong Zhao, Sumin Gu, Jean Xin Jiang, Peng Shang
Osteocytes, the most abundant cells in bone, are highly responsive to external environmental changes. We tested how Cx43 hemichannels which mediate the exchange of small molecules between cells and extracellular environment impact genome wide gene expression under conditions of abnormal gravity and magnetic field. To this end, we subjected osteocytic MLO-Y4 cells to a high magneto-gravitational environment and used microarray to examine global gene expression and a specific blocking antibody was used to assess the role of Cx43 hemichannels...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27814632/implication-of-cd38-gene-in-autophagic-degradation-of-collagen-i-in-mouse-coronary-arterial-myocytes
#9
Jun-Xiang Bao, Qin-Fang Zhang, Mi Wang, Min Xia, Krishna M Boini, Erich Gulbins, Yang Zhang, Pin-Lan Li
Collagen deposition is a hallmark of atherosclerosis. Although compromised collagen I degradation has been implied in the pathogenesis of atherosclerosis, the molecular mechanisms are still unclear. Thus, we determined the role of CD38, an enzyme involved in cellular calcium modulation and autophagic flux, in the regulation of collagen I degradation in coronary arterial myocytes (CAMs).In primary cultured CAMs from CD38(-/-) mice, collagen I protein accumulation but not mRNA abundance was significantly increased compared with cells from CD38(+/+) mice either under control or upon TGF-Beta stimulation...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27814572/tgf-beta1-wnt-and-shh-signaling-in-tumor-progression-and-in-fibrotic-diseases
#10
Maria D Castellone, Mikko O Laukkanen
Activation of resting fibroblasts to myofibroblasts characterizes several physiological and pathological conditions, from wound healing to aggressive metastatic cancers. In tissue damage, including wound healing, fibroblasts are activated in response to injury for a limited period of time to stimulate the healing process. Similar biological mechanisms are maintained in pathological conditions, e.g., scleroderma and cancer, where myofibroblasts persist in producing cytokines and growth factors to drive the development of fibrosis and the progression of disease...
January 1, 2017: Frontiers in Bioscience (Scholar Edition)
https://www.readbyqxmd.com/read/27805817/the-role-of-tgf-beta-and-ppar-alpha-signalling-pathways-in-radiation-response-of-locally-exposed-heart-integrated-global-transcriptomics-and-proteomics-analysis
#11
Vikram Subramanian, Ingar Seemann, Juliane Merl-Pham, Stefanie M Hauck, Fiona Anne Stewart, Michael J Atkinson, Soile Tapio, Omid Azimzadeh
Epidemiological data from patients undergoing radiotherapy for thoracic tumours clearly show the damaging effect of ionising radiation on cardiovascular system. The long-term impairment of heart function and structure after local high-dose irradiation is associated with systemic inflammatory response, contraction impairment, microvascular damage and cardiac fibrosis. The goal of the present study was to investigate molecular mechanisms involved in this process. C57BL/6J mice received a single X-ray dose of 16 Gy given locally to the heart at the age of 8 weeks...
November 2, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/27798640/altered-expression-of-human-smooth-muscle-myosin-phosphatase-targeting-mypt-isovariants-with-pregnancy-and-labor
#12
Jon Lartey, Julie Taggart, Stephen Robson, Michael Taggart
BACKGROUND: Myosin light-chain phosphatase is a trimeric protein that hydrolyses phosphorylated myosin II light chains (MYLII) to cause relaxation in smooth muscle cells including those of the uterus. A major component of the phosphatase is the myosin targeting subunit (MYPT), which directs a catalytic subunit to dephosphorylate MYLII. There are 5 main MYPT family members (MYPT1 (PPP1R12A), MYPT2 (PPP1R12B), MYPT3 (PPP1R16A), myosin binding subunit 85 MBS85 (PPP1R12C) and TIMAP (TGF-beta-inhibited membrane-associated protein (PPP1R16B))...
2016: PloS One
https://www.readbyqxmd.com/read/27795824/loss-of-mgat5a-mediated-n-glycosylation-stimulates-regeneration-in-zebrafish
#13
Wuhong Pei, Sunny C Huang, Lisha Xu, Kade Pettie, María Laura Ceci, Mario Sánchez, Miguel L Allende, Shawn M Burgess
BACKGROUND: We are using genetics to identify genes specifically involved in hearing regeneration. In a large-scale genetic screening, we identified mgat5a, a gene in the N-glycosylation biosynthesis pathway whose activity negatively impacts hair cell regeneration. METHODS: We used a combination of mutant analysis in zebrafish and a hair cell regeneration assay to phenotype the loss of Mgat5a activity in zebrafish. We used pharmacological inhibition of N-glycosylation by swansonine...
2016: Cell Regeneration
https://www.readbyqxmd.com/read/27793775/systemic-and-tumor-th1-and-th2-inflammatory-profile-and-macrophages-in-lung-cancer-influence-of-underlying-chronic-respiratory-disease
#14
Mercè Mateu-Jimenez, Víctor Curull, Lara Pijuan, Albert Sánchez-Font, Hugo Rivera-Ramos, Alberto Rodríguez-Fuster, Rafael Aguiló, Joaquim Gea, Esther Barreiro
INTRODUCTION: Chronic respiratory conditions, especially chronic obstructive pulmonary disease (COPD), and inflammatory events underlie lung cancer (LC). We hypothesized that profiles of T helper 1 and T helper 2 cytokines and type 1 and type 2 macrophages (M1 and M2) are differentially expressed in lung tumors and blood of patients with NSCLC with and without COPD and that the ratio M1/M2 specifically may influence their survival. METHODS: In blood, inflammatory cytokines (determined by enzyme-linked immunosorbent assay) were quantified in 80 patients with LC (60 with LC and COPD [the LC-COPD group] and 20 with LC only [the LC-only group]) and lung specimens (tumor and nontumor) from those undergoing thoracotomy (20 in the LC-COPD group and 20 in the LC-only group)...
October 25, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27793090/left-right-axis-asymmetry-determining-human-cryptic-gene-is-transcriptionally-repressed-by-snail
#15
Kartik Gupta, Vijaya Satish Sekhar Pilli, Gopala Krishna Aradhyam
BACKGROUND: Establishment of the left-right axis is important for positioning organs asymmetrically in the developing vertebrate-embryo. A number of factors like maternally deposited molecules have emerged essential in initiating the specification of the axis; the downstream events, however, are regulated by signal-transduction and gene-expression changes identifying which remains a crucial challenge. The EGF-CFC family member Cryptic, that functions as a co-receptor for some TGF-beta ligands, is developmentally expressed in higher mammals and mutations in the gene cause loss or change in left-right axis asymmetry...
October 28, 2016: BMC Developmental Biology
https://www.readbyqxmd.com/read/27755557/an-abbreviated-protocol-for-in-vitro-generation-of-functional-human-embryonic-stem-cell-derived-beta-like-cells
#16
Mohammad Massumi, Farzaneh Pourasgari, Amarnadh Nalla, Battsetseg Batchuluun, Kristina Nagy, Eric Neely, Rida Gull, Andras Nagy, Michael B Wheeler
The ability to yield glucose-responsive pancreatic beta-cells from human pluripotent stem cells in vitro will facilitate the development of the cell replacement therapies for the treatment of Type 1 Diabetes. Here, through the sequential in vitro targeting of selected signaling pathways, we have developed an abbreviated five-stage protocol (25-30 days) to generate human Embryonic Stem Cell-Derived Beta-like Cells (ES-DBCs). We showed that Geltrex, as an extracellular matrix, could support the generation of ES-DBCs more efficiently than that of the previously described culture systems...
2016: PloS One
https://www.readbyqxmd.com/read/27753900/os-01-09-markers-of-early-renal-impairment-in-prehypertension
#17
Ana Vrdoljak, Vanja Ivković, Sandra Karanović, Živka Dika, Ivana Vuković, Jelena Kos, Mario Laganović, Tajana Željković Vrkić, Margareta Fištrek Prlić, Ivan Pećin, Bojan Jelaković
OBJECTIVE: It was observed that glomerular hyperfiltration (GHF) is associated with progression of kidney disease in diabetics, patients in stage 1 hypertension (HT), and we found previously that eGFR decreased faster also in prehypertensives (PHT) with GHF. Here we analyzed whether GHF in PHT is associated with other biomarkers of early renal impairment. DESIGN AND METHOD: From 954 subjects enrolled in ENAH follow-up study, 371(137 m;mean age = 46years) were eligible for further analysis:100 with optimal,72 with normal BP,70 with PHT(high normal BP),and 129 with newly diagnosed untreated HT...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27753835/sy-05-1-fibro-inflammatory-changes-during-progression-of-systolic-diastolic-dysfunction-in-the-hypertensive-heart
#18
Hisashi Kai
There is increasing evidence that fibro-inflammatory changes play a role in variety of cardiovascular diseases. We created new rat models to investigate the role of fibro-inflammatory changes in the pathophysiology of systolic and diastolic dysfunction in hypertensive heart. (1) a model of a blood pressure (BP) surge was created by performing abdominal aortic constriction in Wistar-Kyoto rats. Aortic constriction rapidly increased BP and the high BP levels sustained. A BP surge transiently induced MCP-1 and TGF-beta induction, angiotensin converting enzyme activation, and macrophage infiltration, followed by left ventricular (LV) hypertrophy and perivascular reactive fibrosis...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27732750/activin-inhibition-limits-early-innate-immune-response-in-rat-kidney-allografts-a-pilot-study
#19
Niina K Palin, Johanna Savikko, Arja Pasternack, Jukka M Rintala, Bhanu Kalra, Shivani Mistry, Ajay Kumar, Marie-Paule Roth, Heikki Helin, Olli Ritvos
BACKGROUND: Activins are members of the TGF-beta superfamily of cytokines. They play critical roles in the onset of acute and chronic inflammatory responses. The aim of this study was to investigate how activin inhibition affects acute kidney injury and inflammation after transplantation. METHODS: The study was done in kidney transplantation and renal ischemia-reperfusion models in the rat. Soluble activin type 2 receptor (sActRIIB-Fc) was used to inhibit activin signaling...
October 12, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/27725197/in%C3%A2-vitro-secretomics-study-of-pterygium-derived-fibroblasts-by-itraq-based-quantitative-proteomics-strategy
#20
Aihua Hou, Kai Pong Law, Min Qi Tin, Yoon Pin Lim, Louis Tong
Pterygium is a triangular shaped ocular fibrous surface lesion growing from conjunctiva towards central cornea, causing ocular irritation, astigmatism, and visual disturbance. The condition is characterized by epithelial proliferation, fibrovascular growth, chronic inflammation, and prominent extracellular matrix remodeling. Studies have suggested that aberrant extracellular proteins secreted by fibroblasts lead to abnormal matrix production and tissue invasion contributing to the development of the disease...
October 8, 2016: Experimental Eye Research
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