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https://www.readbyqxmd.com/read/28427241/egfr-inhibition-attenuates-diabetic-nephropathy-through-decreasing-ros-and-endoplasmic-reticulum-stress
#1
Zheng Xu, Yunjie Zhao, Peng Zhong, Jingying Wang, Qiaoyou Weng, Yuanyuan Qian, Jibo Han, Chunpeng Zou, Guang Liang
Diabetic nephropathy (DN) is a progressive kidney disease due to glomerular capillary damage in diabetic patients. Endoplasmic reticulum (ER) stress caused by reactive oxygen species (ROS) is associated with DN progression. Epidermal growth factor receptor (EGFR) mediates oxidative stress and damage of cardiomyocytes in diabetic mice. Here we demonstrated that AG1478, a specific inhibitor of EGFR, blocked EGFR and AKT phosphorylation in diabetic mice. Oxidative stress and ER stress markers were eliminated after AG1478 administration...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426803/dendritic-cell-maturation-but-not-type-i-interferon-exposure-restricts-infection-by-htlv-1-and-viral-transmission-to-t-cells
#2
Gergès Rizkallah, Sandrine Alais, Nicolas Futsch, Yuetsu Tanaka, Chloé Journo, Renaud Mahieux, Hélène Dutartre
Human T lymphotropic Virus type 1 (HTLV-1) is the etiological agent of Adult T cell Leukemia/Lymphoma (ATLL) and HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). Both CD4+ T-cells and dendritic cells (DCs) infected with HTLV-1 are found in peripheral blood from HTLV-1 carriers. We previously demonstrated that monocyte-derived IL-4 DCs are more susceptible to HTLV-1 infection than autologous primary T-cells, suggesting that DC infection precedes T-cell infection. However, during blood transmission, breast-feeding or sexual transmission, HTLV-1 may encounter different DC subsets present in the blood, the intestinal or genital mucosa respectively...
April 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28426781/tauroursodeoxycholic-acid-tudca-attenuates-pressure-overload-induced-cardiac-remodeling-by-reducing-endoplasmic-reticulum-stress
#3
Shilpa Rani, Pradeep Kumar Sreenivasaiah, Jin Ock Kim, Mi Young Lee, Wan Seok Kang, Yong Sook Kim, Youngkeun Ahn, Woo Jin Park, Chunghee Cho, Do Han Kim
Pressure overload in the heart induces pathological hypertrophy and is associated with cardiac dysfunction. Apoptosis and fibrosis signaling initiated by the endoplasmic reticulum stress (ERS) is known to contribute to these maladaptive effects. The aim of this study was to investigate whether reduction of ERS by a known chemical chaperone, tauroursodeoxycholic acid (TUDCA) can attenuate pressure overload-induced cardiac remodeling in a mouse model of transverse aortic constriction (TAC). Oral administration of TUDCA at a dose of 300 mg/kg body weight (BW) in the TUDCA-TAC group reduced ERS markers (GRP78, p-PERK, and p-eIf2α), compared to the Vehicle (Veh)-TAC group...
2017: PloS One
https://www.readbyqxmd.com/read/28426774/the-role-of-air-pollution-in-myocardial-remodeling
#4
A M de Oliveira-Fonoff, C Mady, F G Pessoa, K C B Fonseca, V M C Salemi, F Fernandes, P H N Saldiva, F J A Ramires
BACKGROUND: Excessive air pollution in urban environments can impact morbidity and mortality. The authors evaluated the role of particulate matter2.5 (PM2.5) in structural, geometric, and functional remodeling in hearts, using an experimental model of myocardial infarction. METHODS AND FINDINGS: Seventy-five rats were divided into 5 groups: control (CG), CG exposed to PM2.5 pollution (CGP), myocardial infarcted group (MI), infarcted group immediately exposed to pollution (IGP-I), and infarcted group previously exposed to pollution and kept exposed after infarction (IGP-II)...
2017: PloS One
https://www.readbyqxmd.com/read/28426742/multiple-components-of-pka-and-tgf-%C3%AE-pathways-are-mutated-in-pseudomyxoma-peritonei
#5
Lilli Saarinen, Pirjo Nummela, Alexandra Thiel, Rainer Lehtonen, Petrus Järvinen, Heikki Järvinen, Lauri A Aaltonen, Anna Lepistö, Sampsa Hautaniemi, Ari Ristimäki
Pseudomyxoma peritonei (PMP) is a subtype of mucinous adenocarcinoma mainly restricted to the peritoneal cavity and most commonly originating from the appendix. The genetic background of PMP is poorly understood and no targeted treatments are currently available for this fatal disease. While RAS signaling pathway is affected in most if not all PMP cases and over half of them also have a mutation in the GNAS gene, other genetic alterations and affected pathways are, to a large degree, poorly known. In this study, we sequenced whole coding genome of nine PMP tumors and paired normal tissues in order to identify additional, commonly mutated genes and signaling pathways affected in PMP...
2017: PloS One
https://www.readbyqxmd.com/read/28426699/anti-il-20-monoclonal-antibody-inhibited-inflammation-and-protected-against-cartilage-destruction-in-murine-models-of-osteoarthritis
#6
Yu-Hsiang Hsu, Ya-Yu Yang, Man-Hsiang Huwang, Yun-Han Weng, I-Ming Jou, Po-Tin Wu, Tain-Yu Lin, Li-Wha Wu, Ming-Shi Chang
Osteoarthritis (OA) is a degenerative joint disease characterized by progressive destruction of articular cartilage. Interleukin (IL)-20 is a proinflammatory cytokine involved in the pathogenesis of rheumatoid arthritis. We investigated the role of IL-20 in OA and evaluated whether anti-IL-20 antibody (7E) treatment attenuates disease severity in murine models of surgery-induced OA. Immunohistochemical staining was used to detect IL-20 and its receptors expression in synovial tissue and cartilage from OA patients, and in OA synovial fibroblasts (OASFs) and chondrocytes (OACCs) from rodents with surgery-induced OA...
2017: PloS One
https://www.readbyqxmd.com/read/28425962/regulation-of-ubiquitin-enzymes-in-the-tgf-%C3%AE-pathway
#7
REVIEW
Prasanna Vasudevan Iyengar
The transforming growth factor-β (TGF-β) pathway has a tumor suppressor role in normal and premalignant cells but promotes oncogenesis in advanced cancer cells. Components of the pathway are tightly controlled by ubiquitin modifying enzymes and aberrations in these enzymes are frequently observed to dysregulate the pathway causing diseases such as bone disorders, cancer and metastasis. These enzymes and their counterparts are increasingly being tested as druggable targets, and thus a deeper understanding of the enzymes is required...
April 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28425576/bone-marrow-adipose-and-lung-tissue-derived-murine-mesenchymal-stromal-cells-release-different-mediators-and-differentially-affect-airway-and-lung-parenchyma-in-experimental-asthma
#8
Soraia C Abreu, Mariana A Antunes, Debora G Xisto, Fernanda F Cruz, Vivian C Branco, Elga Bandeira, Jamil Zola Kitoko, Almair F de Araújo, Ludmilla Dellatorre-Texeira, Priscilla C Olsen, Daniel J Weiss, Bruno L Diaz, Marcelo M Morales, Patricia R M Rocco
Mesenchymal stromal cells (MSCs) from different sources have differential effects on lung injury. To compare the effects of murine MSCs from bone marrow (BM), adipose tissue (AD), and lung tissue (LUNG) on inflammatory and remodeling processes in experimental allergic asthma, female C57BL/6 mice were sensitized and challenged with ovalbumin (OVA) or saline (C). Twenty-four hours after the last challenge, mice received either saline (50 µl, SAL), BM-MSCs, AD-MSCs, or LUNG-MSCs (10(5) cells per mouse in 50 µl total volume) intratracheally...
April 20, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28424623/notch-signaling-in-ischemic-damage-and-fibrosis-evidence-and-clues-from-the-heart
#9
REVIEW
Silvia Nistri, Chiara Sassoli, Daniele Bani
Notch signaling is a major intercellular coordination mechanism highly conserved throughout evolution. In vertebrates, Notch signaling is physiologically involved in embryo development, including mesenchymal cell commitment, formation of heart tissues and angiogenesis. In post-natal life, Notch signaling is maintained as a key mechanism of cell-cell communication and its dysregulations have been found in pathological conditions such as ischemic and fibrotic diseases. In the heart, Notch takes part in the protective response to ischemia, being involved in pre- and post-conditioning, reduction of reperfusion-induced oxidative stress and myocardial damage, and cardiomyogenesis...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28424410/ascites-promotes-cell-migration-through-the-repression-of-mir-125b-in-ovarian-cancer
#10
Lan Yang, Xiaoli Zhang, Yiming Ma, Xinhua Zhao, Bin Li, Hongying Wang
Interactions between ovarian cancer cells and the surrounding tumor microenvironment are not well characterized. Here, we investigated the molecular mechanisms by which malignant ascites promote the metastasis of ovarian cancer. It was found that ovarian cancer ascites promoted ovarian cancer cell migration which was attenuated by either heat inactivation or antibody blockade of TGF-β. High level (at ng/ml level) of TGF-β was detected in the ascites. In addition, ascites repressed the expression of miRNA-125b in a TGF-β-dependent manner...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423685/tumor-fibroblast-interactions-stimulate-tumor-vascularization-by-enhancing-cytokine-driven-production-of-mmp9-by-tumor-cells
#11
Michelle Limoge, Alfiya Safina, Amy Beattie, Lauren Kapus, Alexander M Truskinovsky, Andrei V Bakin
Advance-stage breast carcinomas include significant amounts of fibroblasts and infiltrating immune cells which have been implicated in tumor growth, recurrence, and response to therapy. The present study investigated the contribution of fibroblasts to tumor growth using direct tumor-fibroblast co-cultures and tumor xenograft models. Our findings revealed that fibroblasts enhance breast carcinoma growth by promoting the tumor vasculature via the MMP9-dependent mechanism. In tumor-fibroblast co-cultures, fibroblasts increased expression of TGF-β, TNF, and IL-1β cytokines in tumor cells...
March 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423507/tgf-%C3%AE-independent-ctgf-induction-regulates-cell-adhesion-mediated-drug-resistance-by-increasing-collagen-i-in-hcc
#12
Yeonhwa Song, Jin-Sun Kim, Eun Kyung Choi, Joon Kim, Kang Mo Kim, Haeng Ran Seo
Hepatocellular carcinoma (HCC) is resistant to conventional chemotherapeutic agents and remains an unmet medical need. Here, we demonstrate a mechanism of cell adhesion-mediated drug resistance using a variety of HCC spheroid models to overcome environment-mediated drug resistance in HCC. We classified spheroids into two groups, tightly compacted and loosely compacted aggregates, based on investigation of dynamics of spheroid formation. Our results show that compactness of HCC spheroids correlated with fibroblast-like characteristics, collagen 1A1 (COL1A1) content, and capacity for chemoresistance...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423499/imidazoline-i2-receptor-inhibitor-idazoxan-regulates-the-progression-of-hepatic-fibrosis-via-akt-nrf2-smad2-3-signaling-pathway
#13
Li Xuanfei, Chen Hao, Yi Zhujun, Liu Yanming, Gong Jianping
Liver fibrosis is a global health problem and its relationship with imidazoline I2 receptor has not been reported. This study aimed to investigate the effects and underlying mechanisms of imidazoline I2 receptor (I2R) inhibitor idazoxan (IDA) on carbon tetrachloride (CCl4)-induced liver fibrosis. In vivo liver fibrosis in mice was induced by intraperitoneally injections of CCl4 for eight weeks, and in vitro studies were performed on activated LX2 cells treated with transforming growth factor-β (TGF-β). Our results showed that IDA significantly improved liver inflammation, ameliorated hepatic stellate cells activation and reduced collagen accumulation by suppressing the pro-fibrogenic signaling of TGF-β/Smad...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423340/transforming-growth-factor-%C3%AE-signaling-in-regulatory-t-cells-controls-t-helper-17-cells-and-tissue-specific-immune-responses
#14
Joanne E Konkel, Dunfang Zhang, Peter Zanvit, Cheryl Chia, Tamsin Zangarle-Murray, Wenwen Jin, Songlin Wang, WanJun Chen
Regulatory T cells (Treg cells) perform suppressive functions in disparate tissue environments and against many inflammatory insults, yet the tissue-enriched factor(s) that influence Treg cell phenotype and function remain largely unknown. We have shown a vital role for transforming growth factor-β (TGF-β) signals in safe-guarding specific Treg cell functions. TGF-β signals were dispensable for steady-state Treg cell homeostasis and for Treg cell suppression of T cell proliferation and T helper-1 (Th1) cell differentiation...
April 18, 2017: Immunity
https://www.readbyqxmd.com/read/28423181/mesenteric-lymph-node-cd11b-cd103-pd-l1-high-dendritic-cells-highly-induce-regulatory-t-cells
#15
Aya Shiokawa, Ryutaro Kotaki, Tomohiro Takano, Haruyo Nakajima-Adachi, Satoshi Hachimura
Dendritic cells (DCs) in mesenteric lymph nodes (MLNs) induce Foxp3(+) regulatory T cells to regulate immune responses to beneficial or non-harmful agents in the intestine, such as commensal bacteria and foods. Several studies in MLN DCs have revealed that CD103(+) DC subset highly induces regulatory T cells, and another study has reported that MLN DCs from PD-L1-deficient mice could not induce regulatory T cells. Thus, the present study investigated expression of these molecules on MLN CD11c(+) cells. Four distinct subsets expressing CD103 and/or PD-L1 were identified, namely CD11b(+) CD103(+) PD-L1(High) , CD11b(-) CD103(+) PD-L1(High) , CD11b(-) CD103(+) PD-L1(Low) , and CD11b(+) CD103(-) PD-L1(Int...
April 19, 2017: Immunology
https://www.readbyqxmd.com/read/28421197/ginsenoside-rg1-ameliorates-cigarette-smoke-induced-airway-fibrosis-by-suppressing-the-tgf-%C3%AE-1-smad-pathway-in-vivo-and-in-vitro
#16
Sibin Guan, Qian Liu, Fengfeng Han, Wen Gu, Lin Song, Yue Zhang, Xuejun Guo, Weiguo Xu
Small airway fibrosis is a key pathological process accompanying chronic obstructive pulmonary disease (COPD) and includes fibroblast/myofibroblast transdifferentiation and excessive extracellular matrix deposition. Ginsenoside Rg1, one of the main active ingredients of Panax ginseng, has been shown to exert an antifibrotic effect in many tissues. However, little is known about the underlying mechanism and whether ginsenoside Rg1 can exert an effect on small airway fibrosis. We investigated the anti-small airway fibrosis effects of ginsenoside Rg1 in human embryonic lung fibroblasts and in COPD rats...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28420734/mink1-the-missing-link-between-ros-and-its-inhibition-of-th17-cells
#17
Gustavo J Martinez
In this issue of JEM, Fu et al. (https://doi.org/10.1084/jem.20161120) identified the kinase Mink1 as a novel negative regulator of Th17 cell generation. Mink1, activated by reactive oxygen species (ROS), prevents TGF-β activation of Smad2, therefore limiting Th17 cell differentiation.
April 18, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28420440/immune-response-after-autologous-hematopoietic-stem-cell-transplantation-in-type-1-diabetes-mellitus
#18
Lei Ye, Li Li, Bing Wan, Minglan Yang, Jie Hong, Weiqiong Gu, Weiqing Wang, Guang Ning
BACKGROUND: This study explored the details of the immune response after autologous hematopoietic stem cell transplantation (AHSCT) treatment in type 1 diabetes mellitus. METHODS: Peripheral blood mononuclear cells (PBMCs) from 18 patients with type 1 diabetes mellitus were taken at baseline and 12 months after AHSCT or insulin-only therapy. The lymphocyte proliferation, mRNA expression and secretion of pro-inflammatory and anti-inflammatory cytokines belonging to T-helper type 1 (Th1), T-helper type 17 (Th17) and regulatory T (Treg) cells in PBMC culture supernatants were assessed...
April 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28418584/transforming-growth-factor-%C3%AE-inhibitor-repsox-down-regulates-collagen-expression-of-scleroderma-dermal-fibroblasts-and-prevents-bleomycin-induced-mice-skin-fibrosis
#19
Maho Ide, Masatoshi Jinnin, Yukiko Tomizawa, Zhongzhi Wang, Ikko Kajihara, Satoshi Fukushima, Yoshinobu Hashizume, Yoshihide Asano, Hironobu Ihn
Inhibition of transforming growth factor (TGF)-β1 signaling may be one of the most reliable approaches to treat skin fibrosis of scleroderma. Although there have been a lot of basic researches of TGF-β blockade reagents, few of them was proved to have inhibitory effects on fibrosis both in vitro and in vivo. In the present study, we randomly chose four commercially available low molecular compounds (Repsox, LY2109761, LY364947, and K02288) from TGF-β1 inhibitor library, and compared their anti-fibrotic effects in vitro and in vivo...
April 18, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28418194/accelerated-tumor-metastasis-due-to-ifn%C3%AE-receptor-mediated-dissociation-of-perivascular-cells-from-blood-vessels
#20
Chen Ni, Pan Ma, Liwei Qu, Fan Wu, Junfeng Hao, Ruirui Wang, Yu Lu, Wei Yang, Ulrike Erben, Zhihai Qin
Angiostasis mediated by IFNγ is a key mechanism of anti-tumor immunity; however, the effect of IFNγ on host VEGFA-expressing cells during tumor progression is still elusive. Here, we developed transgenic mice with IFNγ receptor (IFNγR) expression under control of the Vegfa promoter (V-γR). In these mice, the IFNγ responsiveness of VEGFA -expressing cells led to a dramatic growth suppression of transplanted lung carcinoma cells. Surprisingly, increased mortality and tumor metastasis were observed in the tumor-bearing V-γR mice, in comparison to the control wild type and IFNγR-deficient mice...
April 18, 2017: Journal of Pathology
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