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https://www.readbyqxmd.com/read/28433746/transforming-growth-factor-beta-1-signaling-regulates-neuroinflammation-and-apoptosis-in-mild-traumatic-brain-injury
#1
Rachel K Patel, Nithisha Prasad, Ram Kuwar, Debanjan Haldar, P M Abdul-Muneer
Mild Traumatic brain injury (mTBI) is a low-level injury, which often remains undiagnosed, and in most cases it leads to death and disability as it advances as secondary injury. Therefore, it is important to study the underlying signaling mechanisms of mTBI-associated neurological ailments. While transforming growth factor-beta1 (TGF-β1) has a significant role in inflammation and apoptosis in myriads of other pathophysiological conditions, the precise function of increased TGF-β1 after mTBI is unknown. In this study, our objective is to study the physiological relevance and associated mechanisms of TGF-β1-mediated inflammation and apoptosis in mTBI...
April 19, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28418194/accelerated-tumor-metastasis-due-to-ifn%C3%AE-receptor-mediated-dissociation-of-perivascular-cells-from-blood-vessels
#2
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
https://www.readbyqxmd.com/read/28414804/cyclosporine-a-alters-expression-of-renal-micrornas-new-insights-into-calcineurin-inhibitor-nephrotoxicity
#3
Jennifer L Gooch, Clayton King, Cynthia E Francis, Paul S Garcia, Yun Bai
Calcineurin inhibitors are powerful immunosuppressants that revolutionized organ transplantation. However, non-immune effects of the calcineurin inhibitor, such as cyclosporine A (CsA), have significantly hindered their use. Specifically, nephrotoxicity, which is associated with tubulointerstitial fibrosis, inflammation, and podocyte damage, affects up to half of all transplant patients. Calcineurin is involved in many aspects of kidney development and function; therefore, mechanisms of CsA-induced nephrotoxicity are complex and not yet fully understood...
2017: PloS One
https://www.readbyqxmd.com/read/28414040/sars-coronavirus-papain-like-protease-up-regulates-the-collagen-expression-through-non-samd-tgf-%C3%AE-1-signaling
#4
Ching-Ying Wang, Chien-Yi Lu, Shih-Wen Li, Chien-Chen Lai, Chun-Hung Hua, Su-Hua Huang, Ying-Ju Lin, Mann-Jen Hour, Cheng-Wen Lin
SARS coronavirus (CoV) papain-like protease (PLpro) reportedly induced the production of TGF-β1 through p38 MAPK/STAT3-meidated Egr-1-dependent activation (Sci. Rep. 6, 25754). This study investigated the correlation of PLpro-induced TGF-β1 with the expression of Type I collagen in human lung epithelial cells and mouse pulmonary tissues. Specific inhibitors for TGF-βRI, p38 MAPK, MEK, and STAT3 proved that SARS-CoV PLpro induced TGF-β1-dependent up-regulation of Type I collagen in vitro and in vivo. Subcellular localization analysis of SMAD3 and SMAD7 indicated that non-SMAD pathways in TGF-β1 signaling involved in the production of Type I collagen in transfected cells with pSARS-PLpro...
April 13, 2017: Virus Research
https://www.readbyqxmd.com/read/28406769/dexamethasone-effect-on-the-expression-of-transforming-growth-factor-%C3%AE-1-smads-signaling-pathway-in-benign-biliary-stricture-fibroblasts-in-rodent
#5
Ke -Yue Li, Cheng -Xian Shi, Jian -Zhao Huang, Ke -Li Tang
OBJECTIVE: To investigate the effects of dexamethasone on transforming growth factor (TGF)-β1/Smads signaling pathway in benign biliary stricture (BBS) fibroblasts. STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: Guizhou Medical University, Guiyang, Guizhou, China, from January to August 2016. METHODOLOGY: Fibroblasts derived from rabbit BBS model were cultured and identified, then treated by different concentration of dexamethasone (0...
March 2017: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://www.readbyqxmd.com/read/28400336/aspp2-suppresses-invasion-and-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition-by-inhibiting-smad7-degradation-mediated-by-e3-ubiquitin-ligase-itch-in-gastric-cancer
#6
Yasuyuki Gen, Kohichiroh Yasui, Tomoko Kitaichi, Naoto Iwai, Kei Terasaki, Osamu Dohi, Hikaru Hashimoto, Hayato Fukui, Yutaka Inada, Akifumi Fukui, Masayasu Jo, Michihisa Moriguchi, Taichiro Nishikawa, Atushi Umemura, Kanji Yamaguchi, Hiroyuki Konishi, Yuji Naito, Yoshito Itoh
ASPP2 regulates cell polarity and cell-cell adhesion by binding to, and co-localizing with PAR3 at tight junctions. Here we show a novel role of ASPP2 in suppressing gastric cancer (GC) invasiveness. Immunoprecipitation and immunofluorescence analyses showed that ASPP2 promoted the recruitment of PAR3 to cell-cell junctions in GC cells. Diminished expression of ASPP2 and loss of junctional PAR3 localization were significantly associated with diffuse-type histology, deeper invasion depth, positive peritoneal dissemination and worse prognosis in primary GC...
April 9, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28392641/low-level-light-therapy-with-410-nm-light-emitting-diode-suppresses-collagen-synthesis-in-human-keloid-fibroblasts-an-in-vitro-study
#7
Hyun Soo Lee, Soo-Eun Jung, Sue Kyung Kim, You-Sun Kim, Seonghyang Sohn, You Chan Kim
BACKGROUND: Keloids are characterized by excessive collagen deposition in the dermis, in which transforming growth factor β (TGF-β)/Smad signaling plays an important role. Low-level light therapy (LLLT) is reported as effective in preventing keloids in clinical reports, recently. To date, studies investigating the effect of LLLT on keloid fibroblasts are extremely rare. OBJECTIVE: We investigated the effect of LLLT with blue (410 nm), red (630 nm), and infrared (830 nm) light on the collagen synthesis in keloid fibroblasts...
April 2017: Annals of Dermatology
https://www.readbyqxmd.com/read/28382862/inflammatory-bowel-disease-new-therapeutic-options-in-the-post-anti-tnf%C3%AE-era
#8
Miguel Jiménez Pérez, Raúl V Olmedo Martín, Víctor M Amo Trillo, Rocío González Gande
Inflammatory bowel diseasesare chronic bowel disorders the causes of which have not been fully elucidated,though they all sharean immunological basis. They have an important impact on both quality of life of the patient and on healthcare services. The incorporation of biological agents against tumour necrosis factor (TNF) alpha some 15 years ago represented a revolution in the management of patients with disease that did not respond to conventional treatment, enabling an overall improvement in the quality of life of many of these patients...
April 6, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28381482/usp26-regulates-tgf-%C3%AE-signaling-by-deubiquitinating-and-stabilizing-smad7
#9
Sarah Kit Leng Lui, Prasanna Vasudevan Iyengar, Patrick Jaynes, Zul Fazreen Bin Adam Isa, Brendan Pang, Tuan Zea Tan, Pieter Johan Adam Eichhorn
The amplitude of transforming growth factor-β (TGF-β) signal is tightly regulated to ensure appropriate physiological responses. As part of negative feedback loop SMAD7, a direct transcriptional target of downstream TGF-β signaling acts as a scaffold to recruit the E3 ligase SMURF2 to target the TGF-β receptor complex for ubiquitin-mediated degradation. Here, we identify the deubiquitinating enzyme USP26 as a novel integral component of this negative feedback loop. We demonstrate that TGF-β rapidly enhances the expression of USP26 and reinforces SMAD7 stability by limiting the ubiquitin-mediated turnover of SMAD7...
April 5, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28378938/ag490-suppresses-interleukin-34-mediated-osteoclastogenesis-in-mice-bone-marrow-macrophages
#10
Xin Cheng, Qi-Long Wan, Zu-Bing Li
Interleukin-34 (IL-34) has been recently identified as a novel cytokine, substituting for the function of macrophage colony-stimulating factor (M-CSF), a pivotal osteoclastogenic factor involved in bone-related diseases (e.g., osteomyelitis of the jaws). However, the molecular mechanisms are not fully understood. This study aimed to explore the potential mechanism of IL-34 in receptor activator of NF-kB Ligand (RANKL)-induced osteoclast formation. We found that IL-34 alone significantly maintained the survival of bone-marrow macrophages (BMMs) and enhanced the expression of the osteoclast-related genes TRAP, Ctsk, and NFATc1, as well as TRAP-positive multinucleated cells combined with RANKL, which can be reversed by AG490...
April 5, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28374902/impact-of-microrna-375-and-its-target-gene-smad-7-polymorphism-on-susceptibility-of-colorectal-cancer
#11
Olfat Gamil Shaker, Shereen Rashad Mohammed, Asmaa Mohammed Mohammed, Zeinab Mahmoud
BACKGROUND: Colorectal cancer (CRC) has a high morbidity and mortality. Many studies reported that mir-375 is frequently down-regulated in many cancers including esophageal cancer, hepatocellular carcinoma, breast cancer and leukemias. AIM: Our aim was to study the expression of microRNA-375 and its target gene SMAD-7 polymorphisms (rs4939827) in CRC patients in comparison to control subjects and to correlate these results with clinical data of patients to elucidate their role in pathogenesis and early diagnosis of CRC...
April 4, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28364097/-effect-of-lamivudine-and-silymarin-on-liver-fibrosis-relevant-factors-in-hbv-transgenic-mice-with-alcohol-drinking
#12
Juanjuan Huang, Shikun Liu, Zuojun Li, Libo Cao, Linqi Ouyang
To observe the role of lamividine and silymarin preventing and curing liver fibrosis-relevant factors induced by alcohol drinking in hepatitis B virus (HBV) transgenic mice (Tg mice).
 Methods: Forty HBV-Tg BALB/C mice with 1.3 copy were randomly divided into 4 groups: a control group, a model group, a lamivudine group and a silymarin group. Tg mice in control group were treated with normal saline via intragastric administration; Tg-mice in the model group were treated with 50% alcohol (5 mL/kg) once a day via intragastric administration; while Tg-mice in lamivudine group and silymarin group were treated with alcohol (5 mL/kg) plus laminvudine (100 mg/kg) and silymarin (200 mg/kg) once a day via intragastric administration respectively...
March 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/28352366/prolyl-oligopeptidase-attenuates-hepatic-stellate-cell-activation-through-induction-of-smad7-and-ppar-%C3%AE
#13
Da Zhou, Jing Wang, Ling-Nan He, Bing-Hang Li, Yong-Nian Ding, Yuan-Wen Chen, Jian-Gao Fan
Prolyl oligopeptidase (POP) is a serine endopeptidase widely distributed in vivo with high activity in the liver. However, its biological functions in the liver have remained largely elusive. A previous study by our group has shown that POP produced N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) and thereby exerted an anti-fibrogenic effect on hepatic stellate cells (HSCs) in vitro. It was therefore hypothesized that POP may affect the activation state of HSCs and has an important role in liver fibrosis. The HSC-T6 immortalized rat liver stellate cell line was treated with the POP inhibitor S17092 or transfected with recombinant lentivirus to overexpress POP...
February 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28339457/targeted-aav5-smad7-gene-therapy-inhibits-corneal-scarring-in-vivo
#14
Suneel Gupta, Jason T Rodier, Ajay Sharma, Elizabeth A Giuliano, Prashant R Sinha, Nathan P Hesemann, Arkasubhra Ghosh, Rajiv R Mohan
Corneal scarring is due to aberrant activity of the transforming growth factor β (TGFβ) signaling pathway following traumatic, mechanical, infectious, or surgical injury. Altered TGFβ signaling cascade leads to downstream Smad (Suppressor of mothers against decapentaplegic) protein-mediated signaling events that regulate expression of extracellular matrix and myogenic proteins. These events lead to transdifferentiation of keratocytes into myofibroblasts through fibroblasts and often results in permanent corneal scarring...
2017: PloS One
https://www.readbyqxmd.com/read/28300830/smad7-knockdown-activates-protein-kinase-rna-associated-eif2%C3%AE-pathway-leading-to-colon-cancer-cell-death
#15
Veronica De Simone, Gerolamo Bevivino, Silvia Sedda, Roberta Izzo, Federica Laudisi, Vincenzo Dinallo, Eleonora Franzè, Alfredo Colantoni, Angela Ortenzi, Silvia Salvatori, Piero Rossi, Giuseppe S Sica, Massimo C Fantini, Carmine Stolfi, Giovanni Monteleone
Upregulation of Smad7, an inhibitor of transforming growth factor-β1 (TGF-β1), occurs in sporadic colorectal cancer (CRC) and knockdown of Smad7 inhibits CRC cell growth, a phenomenon that associates with decreased expression of cell division cycle 25 homolog A and arrest of cells in the S phase of the cell cycle. These findings occur in CRC cells unresponsive to TGF-β1, thus suggesting the existence of a Smad7-mediated TGF-β1-independent mechanism that controls CRC cell behavior. Here we show that Smad7 inhibition with a specific Smad7 antisense oligonucleotide upregulates eukaryotic translation initiation factor 2α (eIF2α) phosphorylation, a transcription factor involved in the regulation of cell cycle arrest and induction of cell death, and induces activating transcription factor 4 (ATF4) and CCAAT/enhancer binding protein homology protein (CHOP), two downstream targets of eIF2α...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28292929/rnf11-sequestration-of-smurf2-on-membranes-antagonizes-smad7-down-regulation-of-tgf%C3%AE-signaling
#16
Ryan J Malonis, Wenxiang Fu, Mark J Jelcic, Marae Thompson, Brian S Canter, Mary Tsikitis, Francisco J Esteva, Irma Sánchez
The activity of the E3 ligase, Smurf2, is antagonized by an intra-molecular, auto-inhibitory interaction between its C2 and Hect domains. Relief of Smurf2 auto-inhibition is induced by TGFβ and is mediated by the inhibitory SMAD, Smad7. In a proteomic screen for endo-membrane interactants of the RING-domain E3 ligase, Rnf11, we identified Smurf2, among a cohort of Hect E3 ligases previously implicated in TGFβ signaling. Reconstitution of the Smurf2/Rnf11 complex in vitro unexpectedly revealed robust Smurf2 E3 ligase activity, with biochemical properties previously restricted to the Smurf2/Smad7 complex...
March 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28284148/effect-enhancing-and-toxicity-reducing-activity-of-usnic-acid-in-ascitic-tumor-bearing-mice-treated-with-bleomycin
#17
Zu-Qing Su, Yu-Hong Liu, Hui-Zhen Guo, Chao-Yue Sun, Jian-Hui Xie, Yu-Cui Li, Jian-Nan Chen, Xiao-Ping Lai, Zi-Ren Su, Hai-Ming Chen
Usnic acid (UA) can be found in certain lichen species. Growing evidence suggests that UA possesses antitumoral, antioxidative and anti-inflammatory activities. Bleomycin (BLM) is widely used in the treatment of malignant ascites, however, it unexpectedly causes pulmonary fibrosis (PF). Researches show that excessive inflammatory response and oxidative stress in lung tissue is conspicuous causes of BLM-induced PF. Here we investigated mechanism underlying the effect-enhancing and toxicity-reducing activity of UA on H22-bearing mice treated with BLM...
March 8, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28258388/smad7-deficiency-stimulates-m%C3%A3-ller-progenitor-cell-proliferation-during-the-development-of-the-mammalian-retina
#18
Martina Kugler, Anja Schlecht, Rudolf Fuchshofer, Sabrina I Schmitt, Ingo Kleiter, Ludwig Aigner, Ernst R Tamm, Barbara M Braunger
The transforming growth factor-β (TGF-β) pathway contributes to maintain the quiescence of adult neural stem and progenitor cells in the brain. In the retina, Müller cells are discussed to represent a glial cell population with progenitor-like characteristics. Here, we aimed to investigate if elevated TGF-β signaling modulates the proliferation of Müller cells during retinal development. We generated mutant mice with a systemic, heterozygous up-regulation of TGF-β signaling by deleting its inhibitor SMAD7...
March 3, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28254481/effects-of-the-combined-herba-epimedii-and-fructus-ligustri-lucidi-on-bone-turnover-and-tgf-%C3%AE-1-smads-pathway-in-giop-rats
#19
Yan Yang, Honglei Nian, Xiufeng Tang, Xiujuan Wang, Renhui Liu
ETHNOPHARMACOLOGICAL RELEVANCE: Kidney deficiency is the main pathogenesis of osteoporosis based on the theory of "kidney governing bones" in traditional Chinese medicine (TCM). Combined Herba Epimedii and Fructus Ligustri Lucidi, based on traditional Chinese formula Er-Zhi pills, were frequently used in TCM formulas that were prescribed for kidney tonifying and bone strengthening. However, it is unclear whether the combination of the two herbs may have a protective influence on glucocorticoid-induced osteoporosis (GIOP)...
February 27, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28230206/mirna-21-mediates-the-antiangiogenic-activity-of-metformin-through-targeting-pten-and-smad7-expression-and-pi3k-akt-pathway
#20
Mao Luo, Xiaoyong Tan, Lin Mu, Yulin Luo, Rong Li, Xin Deng, Ni Chen, Meiping Ren, Yongjie Li, Liqun Wang, Jianbo Wu, Qin Wan
Metformin, an anti-diabetic drug commonly used for type 2 diabetes therapy, is associated with anti-angiogenic effects in conditions beyond diabetes. miR-21 has been reported to be involved in the process of angiogenesis. However, the precise regulatory mechanisms by which the metformin-induced endothelial suppression and its effects on miR-21-dependent pathways are still unclear. Bioinformatic analysis and identification of miR-21 and its targets and their effects on metformin-induced antiangiogenic activity were assessed using luciferase assays, quantitative real-time PCR, western blots, scratch assays, CCK-8 assays and tubule formation assays...
February 23, 2017: Scientific Reports
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