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https://www.readbyqxmd.com/read/28821630/il-17a-deficiency-mitigates-bleomycin-induced-complement-activation-during-lung-fibrosis
#1
Ellyse Cipolla, Amanda J Fisher, Hongmei Gu, Elizabeth A Mickler, Manisha Agarwal, Carol A Wilke, Kevin K Kim, Bethany B Moore, Ragini Vittal
Interleukin 17A (IL-17A) and complement (C') activation have each been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). We have reported that IL-17A induces epithelial injury via TGF-β in murine bronchiolitis obliterans; that TGF-β and the C' cascade present signaling interactions in mediating epithelial injury; and that the blockade of C' receptors mitigates lung fibrosis. In the present study, we investigated the role of IL-17A in regulating C' in lung fibrosis. Microarray analyses of mRNA isolated from primary normal human small airway epithelial cells indicated that IL-17A (100 ng/ml; 24 h; n = 5 donor lungs) induces C' components (C' factor B, C3, and GPCR kinase isoform 5), cytokines (IL8, -6, and -1B), and cytokine ligands (CXCL1, -2, -3, -5, -6, and -16)...
August 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28821620/arjunolic-acid-a-peroxisome-proliferator-activated-receptor-alpha-agonist-regresses-cardiac-fibrosis-by-inhibiting-non-canonical-tgf-%C3%AE-signaling
#2
Trisha Bansal, Emeli Chatterjee, Jasdeep Singh, Arjun Ray, Bishwajit Kundu, V Thankamani, Shantanu Sengupta, Sagartirtha Sarkar
Cardiac hypertrophy and associated heart fibrosis remain a major cause of death worldwide. Phytochemicals have gained attention as alternative therapeutics for managing cardiovascular diseases. These include the extract from the plant Terminalia arjuna which is a popular cardioprotectant and may prevent or slow progression of pathological hypertrophy to heart failure. Here, we investigated the mode of action of a principal bioactive T. arjuna compound, arjunolic acid (AA) in ameliorating hemodynamic load-induced cardiac fibrosis and identified its intracellular target...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821477/tgf-%C3%AE-induced-intracellular-pai-1-is-responsible-for-retaining-hematopoietic-stem-cells-in-the-niche
#3
Takashi Yahata, Abd Aziz Ibrahim, Yukari Muguruma, Mesut Eren, Alexander M Shaffer, Nobuo Watanabe, Satoko Kaneko, Tetsuo Nakabayashi, Takashi Dan, Noriaki Hirayama, Douglas E Vaughan, Toshio Miyata, Kiyoshi Ando
Hematopoietic stem and progenitor cells (HSPCs) reside in the supportive stromal niche in bone marrow (BM); when needed, however, they are rapidly mobilized into the circulation, suggesting that HSPCs are intrinsically highly motile but are usually stayed in the niche. We questioned what determines the motility of HSPCs. Here we show that transforming growth factor (TGF)-β-induced intracellular plasminogen activator inhibitor (PAI)-1 activation is responsible for keeping HSPCs in the BM niche. We found that the expression of PAI-1, a downstream target of TGF-β-signaling, was selectively augmented in niche-residing HSPCs...
August 18, 2017: Blood
https://www.readbyqxmd.com/read/28821451/5-ht7-receptor-antagonism-sb-269970-attenuates-bleomycin-induced-pulmonary-fibrosis-in-rats-via-downregulating-oxidative-burden-and-inflammatory-cascades-and-ameliorating-collagen-deposition-comparison-to-terguride
#4
Mona K Tawfik, Samy Makary
The neurotransmitter 5-hydroxytryptamine (5-HT) is involved in regulation of local tissue inflammation and repair through a set of receptors (5-HT1-7 receptors), which are expressed in the lung. Considering the protective importance of 5-HT receptor antagonists against development of pulmonary fibrosis, we evaluated whether 5-HT7 receptor antagonist (SB-269970) modulates lung inflammatory and fibrogenic processes in comparison with 5-HT2A/B receptor antagonist (terguride), in bleomycin (BLM)-induced idiopathic pulmonary fibrosis (IPF) model...
August 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28820530/cxcr7-attenuates-the-tgf-%C3%AE-induced-endothelial-to-mesenchymal-transition-and-pulmonary-fibrosis
#5
Shuhong Guan, Jun Zhou
Lung fibrosis is a progressive and often fatal lung disease characterized by fibroblast proliferation and excessive deposition of extracellular matrix in the lungs. The chemokine receptor CXCR7 has been shown to control cell adhesion, migration and proliferation by regulating the epithelial-to-mesenchymal transition (EMT), but the role of CXCR7 in regulating the endothelial-to-mesenchymal transition (EndMT) and lung fibrosis remains largely unclear. In this study, we investigated the interrelation of CXCR7 and TGF-β, a crucial player in lung fibrogenesis...
August 18, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28820432/rho-kinase-blockade-attenuates-podocyte-apoptosis-by-inhibiting-the-notch-signaling-pathway-in-diabetic-nephropathy
#6
Keiichiro Matoba, Daiji Kawanami, Yosuke Nagai, Yusuke Takeda, Tomoyo Akamine, Sho Ishizawa, Yasushi Kanazawa, Tamotsu Yokota, Kazunori Utsunomiya
Podocyte apoptosis is a key process in the onset of diabetic nephropathy. A significant body of evidence shows that the Notch signaling pathway plays a central role in this process. We found that Rho-kinase mediates transforming growth factor β (TGF-β)-induced Notch ligand Jag1 expression. Importantly, TGF-β-mediated podocyte apoptosis was attenuated by Rho-kinase inhibition. Mechanistically, Rho-kinase regulated Jag1 induction via the extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) but not Smad pathways...
August 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28820083/threonine-deficiency-decreased-intestinal-immunity-and-aggravated-inflammation-associated-with-nf-%C3%AE%C2%BAb-and-target-of-rapamycin-signalling-pathways-in-juvenile-grass-carp-ctenopharyngodon-idella-after-infection-with-aeromonas-hydrophila
#7
Yu-Wen Dong, Wei-Dan Jiang, Yang Liu, Pei Wu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xiao-Qiu Zhou, Lin Feng
This study aimed to investigate the impacts of dietary threonine on intestinal immunity and inflammation in juvenile grass carp. Six iso-nitrogenous semi-purified diets containing graded levels of threonine (3·99-21·66 g threonine/kg) were formulated and fed to fishes for 8 weeks, and then challenged with Aeromonas hydrophila for 14 d. Results showed that, compared with optimum threonine supplementation, threonine deficiency (1) decreased the ability of fish against enteritis, intestinal lysozyme activities (except in the distal intestine), acid phosphatase activities, complement 3 (C3) and C4 contents and IgM contents (except in the proximal intestine (PI)), and it down-regulated the transcript abundances of liver-expressed antimicrobial peptide (LEAP)-2A, LEAP-2B, hepcidin, IgZ, IgM and β-defensin1 (except in the PI) (P<0·05); (2) could up-regulate intestinal pro-inflammatory cytokines TNF-α, IL-1β, IL-6, IL-8 and IL-17D mRNA levels partly related to NF-κB signalling; (3) could down-regulate intestinal anti-inflammatory cytokine transforming growth factor (TGF)-β1, TGF-β2, IL-4/13A (not IL-4/13B) and IL-10 mRNA levels partly by target of rapamycin signalling...
July 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/28819943/the-mmp-9-timp-1-imbalance-and-the-reduced-level-of-tgf-%C3%AE-in-the-cervical-area-of-amniotic-membrane-is-a-possible-risk-factor-of-prom-and-premature-labor-proof-of-concept-study
#8
Małgorzata Litwiniuk, Małgorzata Radowicka, Alicja Krejner, Mirosław Wielgoś, Tomasz Grzela
OBJECTIVES: To assess the level MMP-9, TIMP-1 and TGF-β in placental and cervical region of amniotic membranes derived from at-term, pre-term and PROM deliveries. MATERIAL AND METHODS: 14 amniotic membranes have been assessed; the quantitative analysis of MMP-9, TGF-β and TIMP-1 was assayed using respective Quantikine Immunoassay Kit. RESULTS: The MMP-9 level in PROM samples was similar to the level of MMP-9 in at-term membranes and comparable between the cervical and placental region of these membranes...
2017: Ginekologia Polska
https://www.readbyqxmd.com/read/28819748/lipoxin-a4-attenuates-bronchopulmonary-dysplasia-via-upregulation-of-let-7c-and-downregulation-of-tgf-%C3%AE-1-signaling-pathway
#9
Xiao-Qing Chen, Sheng-Hua Wu, Yan-Yan Luo, Bing-Jie Li, Shu-Jun Li, Hong-Yan Lu, Rui Jin, Zhong-Yi Sun
Transforming growth factor-β (TGF-β) superfamily members are key regulators for lung development and progress of bronchopulmonary dysplasia (BPD). The mechanisms by which lipoxin A4 (LXA4) attenuates development of BPD have not been clarified. Neonatal murine BPD models were inducted by hyperoxia treatment. Neonatal mice were exposed to room air or 85% O2 hyperoxia with or without treatment with 5S,6R-methyl-LXA4 or anti-TGF-β antibodies. Mouse lung epithelial cells (MLE-12 cells) and mouse embryonic fibroblasts (NIH/3T3 cells) were cultured in room air or 85% O2 followed by treatment of LXA4, anti-TGF-β antibodies, and let-7c mimic/anti-microRNA transfections...
August 17, 2017: Inflammation
https://www.readbyqxmd.com/read/28819404/activin-b-regulates-adhesion-invasiveness-and-migratory-activities-in-oral-cancer-a-potential-biomarker-for-metastasis
#10
Akihiro Kita, Atsushi Kasamatsu, Dai Nakashima, Yosuke Endo-Sakamoto, Sho Ishida, Toshihiro Shimizu, Yasushi Kimura, Isao Miyamoto, Shusaku Yoshimura, Masashi Shiiba, Hideki Tanzawa, Katsuhiro Uzawa
Activin B, a homodimer of inhibin beta b (INHBB), is a multifunctional cytokine belonging to the transforming growth factor-β (TGF-β) family. However, the molecular functions and clinical relevance of activin B have not been determined in oral cancer. We investigated the critical roles of activin B in oral squamous cell carcinoma (OSCC). We performed quantitative reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry to study INHBB expression in OSCC-derived cell lines and OSCC clinical samples...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819200/periostin-binding-dna-aptamer-treatment-attenuates-renal-fibrosis-under-diabetic-conditions
#11
Jae Eun Um, Jung Tak Park, Bo Young Nam, Jung Pyo Lee, Jong Ha Jung, Youndong Kim, Seonghun Kim, Jimin Park, Meiyan Wu, Seung Hyeok Han, Tae-Hyun Yoo, Shin-Wook Kang
Diabetic nephropathy, the major cause of chronic kidney disease, is associated with progressive renal fibrosis. Recently, accumulation of periostin, an extracellular matrix protein, was shown to augment renal fibrosis. Aptamers have higher binding affinities without developing the common side effects of antibodies. Thus, we evaluated the effect of periostin inhibition by an aptamer-based inhibitor on renal fibrosis under diabetic conditions. In vitro, transforming growth factor-β1 (TGF-β1) treatment significantly upregulated periostin, fibronectin, and type I collagen mRNA and protein expressions in inner medullary collecting duct (IMCD) cells...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819176/use-of-biocompatible-sorafenib-gold-nanoconjugates-for-reversal-of-drug-resistance-in-human-hepatoblatoma-cells
#12
Sandeep Kumar Vishwakarma, Priyanka Sharmila, Avinash Bardia, Lakkireddy Chandrakala, N Raju, G Sravani, B V S Sastry, Md Aejaz Habeeb, Aleem Ahmed Khan, Marshal Dhayal
The present study identifies the potential of highly biocompatible SF-GNP nano-conjugate to enhance the chemotherapeutic response to combat drug resistance in cancer cells. We developed a stable colloidal suspension of sorafenib-gold nanoconjugate (SF-GNP) of <10 nm size in aqueous medium for reverting the cancer drug resistance in SF-resistant HepG2 cells in a 3D ex-vivo model system. In-vivo biocompatibility assay of SF-GNPs showed absence of systemic toxicological effects including hematological, biochemical and histological parameters...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819169/cd206-m2-like-macrophages-regulate-systemic-glucose-metabolism-by-inhibiting-proliferation-of-adipocyte-progenitors
#13
Allah Nawaz, Aminuddin Aminuddin, Tomonobu Kado, Akiko Takikawa, Seiji Yamamoto, Koichi Tsuneyama, Yoshiko Igarashi, Masashi Ikutani, Yasuhiro Nishida, Yoshinori Nagai, Kiyoshi Takatsu, Johji Imura, Masakiyo Sasahara, Yukiko Okazaki, Kohjiro Ueki, Tadashi Okamura, Kumpei Tokuyama, Akira Ando, Michihiro Matsumoto, Hisashi Mori, Takashi Nakagawa, Norihiko Kobayashi, Kumiko Saeki, Isao Usui, Shiho Fujisaka, Kazuyuki Tobe
Adipose tissue resident macrophages have important roles in the maintenance of tissue homeostasis and regulate insulin sensitivity for example by secreting pro-inflammatory or anti-inflammatory cytokines. Here, we show that M2-like macrophages in adipose tissue regulate systemic glucose homeostasis by inhibiting adipocyte progenitor proliferation via the CD206/TGFβ signaling pathway. We show that adipose tissue CD206(+) cells are primarily M2-like macrophages, and ablation of CD206(+) M2-like macrophages improves systemic insulin sensitivity, which was associated with an increased number of smaller adipocytes...
August 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28819166/histone-protein-deacetylase-11-targeting-promotes-foxp3-treg-function
#14
Jianbing Huang, Liqing Wang, Satinder Dahiya, Ulf H Beier, Rongxiang Han, Arabinda Samanta, Joel Bergman, Eduardo M Sotomayor, Edward Seto, Alan P Kozikowski, Wayne W Hancock
Current interest in Foxp3+ T-regulatory (Treg) cells as therapeutic targets in transplantation is largely focused on their harvesting pre-transplant, expansion and infusion post-transplantation. An alternate strategy of pharmacologic modulation of Treg function using histone/protein deacetylase inhibitors (HDACi) may allow more titratable and longer-term dosing. However, the effects of broadly acting HDACi vary, such that HDAC isoform-selective targeting is likely required. We report data from mice with constitutive or conditional deletion of HDAC11 within Foxp3+ Treg cells, and their use, along with small molecule HDAC11 inhibitors, in allograft models...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819126/targeted-blockade-of-tgf-%C3%AE-and-il-6-jak2-stat3-pathways-inhibits-lung-cancer-growth-promoted-by-bone-marrow-derived-myofibroblasts
#15
Jindong Shi, Jingjing Feng, Juan Xie, Zhoufang Mei, Tianyun Shi, Shengmei Wang, Yong Du, Gong Yang, Yougen Wu, Xiaojiao Cheng, Shanqun Li, Liming Zhu, Chung S Yang, Shuiping Tu, Zhijun Jie
To investigate the role of TGF-β and IL-6 in myofibroblasts (MFs) - lung cancer cell interactions, lung cancer cells (Lewis and CTM-167 cell lines) were stimulated by IL-6, MF-conditioned medium (MF-CM) or MFs, with or without TGF-β signaling inhibitor - SB431542 and/or JAK2/STAT3 inhibitor - JSI-124. MFs were stimulated by TGF-β, cancer cell-CM or cancer cells, with or without SB431542 and JSI-124. Cell proliferation, the levels of cytokines, expression of mRNA and protein were determined. Mice bearing xenograft tumors were intraperitoneally treated with SB431542 or JSI-124 and monitored for up to 45 days...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819116/silencing-of-tgf-%C3%AE-1-in-tumor-cells-impacts-mmp-9-in-tumor-microenvironment
#16
Lakisha D Moore-Smith, Tatyana Isayeva, Joo Hyoung Lee, Andra Frost, Selvarangan Ponnazhagan
Transforming growth factor (TGF)-β1 contributes to autocrine and paracrine functions in the tumor microenvironment (TME). The present study examined the effects of TGF-β1 crosstalk in TME and its role in mediating tumor formation and progression by targeted abrogation of TGF-β1 expression in metastatic cells in situ. Using species-specific primers, we found a significant increase in MMP-9 gene expression in the tumor-reactive stroma during late-stage metastasis in the lung. This effect was also confirmed in cancer-associated fibroblasts (CAFs) when co-cultured with the tumor cells...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28817954/dissecting-amyloid-beta-deposition-using-distinct-strains-of-the-neurotropic-parasite-toxoplasma-gondii-as-a-novel-tool
#17
Carla M Cabral, Kathryn E McGovern, Wes R MacDonald, Jenna Franco, Anita A Koshy
Genetic and pathologic data suggest that amyloid beta (Aβ), produced by processing of the amyloid precursor protein, is a major initiator of Alzheimer's disease (AD). To gain new insights into Aβ modulation, we sought to harness the power of the coevolution between the neurotropic parasite Toxoplasma gondii and the mammalian brain. Two prior studies attributed Toxoplasma-associated protection against Aβ to increases in anti-inflammatory cytokines (TGF-β and IL-10) and infiltrating phagocytic monocytes. These studies only used one Toxoplasma strain making it difficult to determine if the noted changes were associated with Aβ protection or simply infection...
July 2017: ASN Neuro
https://www.readbyqxmd.com/read/28817834/mdm2-promotes-epithelial-mesenchymal-transition-and-metastasis-of-ovarian-cancer-skov3-cells
#18
Ying Chen, Dan-Dan Wang, Ye-Ping Wu, Dan Su, Tian-Yi Zhou, Ren-Hua Gai, Ying-Ying Fu, Lin Zheng, Qiao-Jun He, Hong Zhu, Bo Yang
BACKGROUND: Metastasis accounts for the most lethal reason for the death of ovarian cancer patients, but remains largely untreated. Epithelial-mesenchymal transition (EMT) is critical for the conversion of early-stage ovarian tumours into metastatic malignancies. Thus the exploration of the signalling pathways promoting EMT would open potential opportunities for the treatment of metastatic ovarian cancer. Herein, the putative role of MDM2 in regulating EMT and metastasis of ovarian cancer SKOV3 cells was investigated...
August 17, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28817830/microrna-200a-inhibits-transforming-growth-factor-%C3%AE-1-induced-proximal-tubular-epithelial-mesenchymal-transition-by-targeting-%C3%AE-catenin
#19
Yi Gong, Zhexue Qin, Baoshang Zhou, Hua Chen, Zhengmin Shi, Jing Zhang
BACKGROUND: The epithelial-mesenchymal transition (EMT) is a crucial event in the development of renal interstitial fibrosis (RIF). A growing body of evidence indicates that β-catenin plays an important role in various types of fibrosis. Although members of the microRNA (miRNA)-200 family have been suggested to suppress EMT in cancer and fibrosis, the function of miRNA-200a in regulating the progression of RIF is unknown. We speculate that miRNA-200a may hinder this progression through the suppression of β-catenin...
August 18, 2017: Nephron
https://www.readbyqxmd.com/read/28817810/tgf-%C3%AE-1-is-involved-in-vitamin-d-induced-chondrogenic-differentiation-of-bone-marrow-derived-mesenchymal-stem-cells-by-regulating-the-erk-jnk-pathway
#20
Xiaorui Jiang, Botao Huang, Huiying Yang, Guishi Li, Chunlei Zhang, Guangshi Yang, Feng Lin, Guodong Lin
BACKGROUND/AIMS: Osteoarthritis (OA) is characterized by degradation of cartilage, sole cell type of which is chondrocytes. Bone marrow-derived mesenchymal stem cells (BMSCs) possess multipotency and can be directionally differentiated into chondrocytes under stimulation. This study was aimed to explore the possible roles of vitamin D and transforming growth factor-β1 (TGF-β1) in the chondrogenic differentiation of BMSCs. METHODS: BMSCs were isolated from femurs and tibias of rats and characterized by flow cytometry...
August 16, 2017: Cellular Physiology and Biochemistry
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