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Smad3

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https://www.readbyqxmd.com/read/29140787/tgf-%C3%AE-requires-the-activation-of-canonical-and-non-canonical-signalling-pathways-to-induce-skeletal-muscle-atrophy
#1
Johanna Ábrigo, Fabian Campos, Felipe Simon, Claudia Riedel, Daniel Cabrera, Cristian Vilos, Claudio Cabello-Verrugio
The transforming growth factor type beta (TGF-β) induces skeletal muscle atrophy characterized by a decrease in fiber's diameter and levels of myosin heavy chain (MHC), also as an increase of MuRF-1 expression. In addition, TGF-β induces muscle atrophy by a mechanism dependent on reactive oxygen species (ROS). TGF-β signals by activating both canonical Smad-dependent, and non-canonical signalling pathways such as ERK1/2, JNK1/2, and p38 MAPKs. However, the participation of canonical and non-canonical signalling pathways in the TGF-β atrophic effect on skeletal muscle is unknown...
August 28, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/29140406/smad3-stat3-crosstalk-in-pathophysiological-contexts
#2
Yuka Itoh, Masao Saitoh, Keiji Miyazawa
Smad3 and STAT3 are intracellular molecules that transmit signals from plasma membrane receptors to the nucleus. Smad3 operates downstream of growth/differentiation factors that utilize activin receptor-like kinase (ALK)-4, 5, or 7, such as transforming growth factor-β (TGF-β), activin, and myostatin. STAT3 principally functions downstream of cytokines that exert their effects via gp130 and Janus family kinases, including interleukin-6 (IL-6), leukemia inhibitory factor (LIF), and oncostatin M. Accumulating evidence indicates that Smad3 and STAT3 engage in crosstalk in a highly context-dependent fashion, cooperating in some conditions while acting antagonistically each other in others...
November 13, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29137393/synergistic-effect-of-eribulin-and-cdk-inhibition-for-the-treatment-of-triple-negative-breast-cancer
#3
Shreyas S Rao, Jenna Stoehr, Danijela Dokic, Lei Wan, Joseph T Decker, Kristine Konopka, Alexandra L Thomas, Jia Wu, Virginia G Kaklamani, Lonnie D Shea, Jacqueline S Jeruss
Activation of CDK2 in triple negative breast cancer (TNBC) can contribute to non-canonical phosphorylation of a TGFβ signaling component, Smad3, promoting cell proliferation and migration. Inhibition of CDK2 was shown to decrease breast cancer oncogenesis. Eribulin chemotherapy was used effectively in the treatment of TNBC. To this end, we tested therapeutic efficacy of a novel CDK2/9 inhibitor, CYC065, eribulin, and the combination of CYC065 and eribulin in 3 different TNBC cell lines, and an in vivo xenograft model...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136085/tgf-beta1-from-endometriomas-promotes-fibrosis-in-surrounding-ovarian-tissues-via-smad2-3-signaling
#4
Li Bing Shi, Feng Zhou, Hai Yan Zhu, Dong Huang, Xiao Ying Jin, Chao Li, Yongdong Dai, Yi Bin Pan, Song Ying Zhang
To elucidate whether the endometriotic cells of endometriomas synthesize transforming growth factor beta1 (TGF-beta1) and understand how it affects surrounding ovarian tissue. We collected biopsies of the cystic walls from 42 endometriomas and 29 mature teratomas and compared mRNA and protein expression of fibrosis-related factors between the cystic walls. Then we detected TGFB1 mRNA synthesis in endometriomas, and tested TGF-beta1 fibrotic effect in vitro. Moreover, we verified the expression of Smad2/3 Signaling components in the endometriotic cystic wall in order to understand whether TGF-beta1/Smad signaling is involved in fibrosis formation of the tissue surrounding endometriomas...
November 10, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29130642/dual-inhibition-of-dnmts-and-ezh2-can-overcome-both-intrinsic-and-acquired-resistance-of-myeloma-cells-to-imids-in-a-cereblon-independent-manner
#5
Konstantinos Dimopoulos, Alexandra Søgaard Helbo, Helga Fibiger Munch-Petersen, Lene Sjö, Jesper Christensen, Lasse Sommer Kristensen, Fazila Asmar, Emil Hermansen, Casey O'Connel, Peter Gimsing, Gangning Liang, Kirsten Grønbaek
Thalidomide and its derivatives, lenalidomide and pomalidomide (also known as IMiDs), have significantly changed the treatment landscape of multiple myeloma, and the recent discovery of cereblon (CRBN) as their direct biological target has led to a deeper understanding of their complex mechanism of action. In an effort to comprehend the precise mechanisms behind the development of IMiD resistance and examine whether it is potentially reversible, we established lenalidomide- (-LR) and pomalidomide-resistant (-PR) human myeloma cell lines from two IMiD-sensitive cell lines, OPM2 and NCI-H929, by continuous culture in the presence of lenalidomide or pomalidomide for 4-6 months, until acquirement of stable resistance...
November 11, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/29128099/regulation-of-cellular-senescence-by-mir-34a-in-alcoholic-liver-injury
#6
Ying Wan, Kelly McDaniel, Nan Wu, Sugeily Ramos-Lorenzo, Trenton Glaser, Julie Venter, Heather Francis, Lindsey Kennedy, Keisaku Sato, Tianhao Zhou, Konstantina Kyritsi, Qiaobing Huang, Tami Annable, Chaodong Wu, Shannon Glaser, Gianfranco Alpini, Fanyin Meng
Alcoholic liver disease remains a major cause of liver-related morbidity and mortality, which ranges from alcoholic steatohepatitis to fibrosis/cirrhosis and hepatocellular carcinoma, and the related mechanisms are understood poorly. In this study, we aimed to investigate the role of miR-34a in alcohol-induced cellular senescence and liver fibrosis. We found that hepatic miR-34a expression was upregulated in ethanol-fed mice and heavy drinkers with steatohepatitis compared with respective controls. Mice treated with miR-34a Vivo-Morpholino developed less severe liver fibrosis than wild-type mice after 5 weeks of ethanol feeding...
November 2, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29127033/the-role-of-tgf%C3%AE-receptor-1-smad3-signaling-in-regulating-the-osteoclastic-mode-caused-by-fluoride
#7
Haolan Yu, Ningning Jiang, XiuHua Yu, Zhitao Zhao, Xiuyun Zhang, Hui Xu
Studies that have focused on the role TGFβ signaling plays in osteoclast activity are gradually increasing; however, literature is rare in terms of fluorosis. The aim of this study is to observe the role the TβR1/Smad3 pathway plays in fluoride regulating cellsosteoclast-like cells that are under the treatment of TGFβ receptor 1 kinase. The RANKL-mediated osteoclast-like cells from RAW264.7 cells were used as osteoclast precursor model. The profile of miRNA expression in fluoride-treated osteoclast-like cells exhibited 303 upregulated miRNAs, 61 downregulated miRNAs, and further drew 37 signaling pathway maps by KEGG and Biocarta pathway enrichment analysis...
November 7, 2017: Toxicology
https://www.readbyqxmd.com/read/29126441/tgf%C3%AE-3-recruits-endogenous-mesenchymal-stem-cells-to-initiate-bone-regeneration
#8
Moyuan Deng, Tieniu Mei, Tianyong Hou, Keyu Luo, Fei Luo, Aijun Yang, Bo Yu, Hao Pang, Shiwu Dong, Jianzhong Xu
BACKGROUND: The recruitment of a sufficient number of endogenous mesenchymal stem cells (MSCs) is the first stage of in-situ tissue regeneration. Transforming growth factor beta-3 (TGFβ3) could recruit stem or progenitor cells and endothelial cells to participate in tissue regeneration. However, the mechanism of TGFβ3 recruiting MSCs toward bone regeneration has remained obscure. METHODS: We estimated the promigratory property of TGFβ3 on human bone marrow MSCs (hBMSCs) cocultured with the vascular cells (human umbilical artery smooth muscle cells or human umbilical vein endothelial cells) or not by Transwell assay...
November 10, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29123266/sox5-contributes-to-prostate-cancer-metastasis-and-is-a-master-regulator-of-tgf-%C3%AE-induced-epithelial-mesenchymal-transition-through-controlling-twist1-expression
#9
Jieping Hu, Jing Tian, Shimiao Zhu, Libin Sun, Jianpeng Yu, Hao Tian, Qian Dong, Qiang Luo, Ning Jiang, Yuanjie Niu, Zhiqun Shang
BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) is one of the main contributors to the death of prostate cancer patients. To date, the detailed molecular mechanisms underlying mCRPC are unclear. Given the crucial role of epithelial-mesenchymal transition (EMT) in cancer metastasis, we aimed to analyse the expression and function of Transforming growth factor-beta (TGF-β) signal-associated protein named Sox5 in mCRPC. METHODS: The protein expression levels were analysed by western blot, immunohistochemistry and immunofluorescence...
November 9, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29116196/thalidomide-inhibits-tgf-%C3%AE-1-induced-epithelial-to-mesenchymal-transition-in-alveolar-epithelial-cells-via-smad-dependent-and-smad-independent-signaling-pathways
#10
Xian-Long Zhou, Peng Xu, Hai-Hua Chen, Yan Zhao, Jun Shen, Cheng Jiang, Shan Jiang, Shao-Zhou Ni, Bing Xu, Lei Li
Recent evidence indicates that the epithelial to mesenchymal transition (EMT) in primary alveolar cells (AECs) plays an important role in idiopathic pulmonary fibrosis (IPF). In vivo models have suggested that thalidomide (THL) has anti-fibrotic effects against pulmonary fibrosis, but the underlying mechanism of this effect is not clear. This study investigated whether THL regulates alveolar EMT and the possible mechanisms underlying this process. CCL-149 cells were treated with TGF-β1 in the presence of THL at the indicated concentrations...
November 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29115576/genome-wide-dna-methylome-alterations-in-acute-coronary-syndrome
#11
Dandan Li, Jing Yan, Yunlong Yuan, Cheng Wang, Jia Wu, Qingwen Chen, Jiaxi Song, Junjun Wang
Acute coronary syndrome (ACS) is a common disease with high mortality and morbidity rates. The methylation status of blood DNA may serve as a potential early diagnosis and prevention biomarker for numerous diseases. The present study was designed to explore novel genome-wide aberrant DNA methylation patterns associated with ACS. The Infinium HumanMethylation450 assay was used to examine genome-wide DNA methylation profiles in 3 pairs of ACS and control group samples. Epigenome-wide DNA methylation, genomic distribution, Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed...
October 27, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29114233/the-jnk-signaling-pathway-in-renal-fibrosis
#12
REVIEW
Keren Grynberg, Frank Y Ma, David J Nikolic-Paterson
Fibrosis of the glomerular and tubulointerstitial compartments is a common feature of chronic kidney disease leading to end-stage renal failure. This fibrotic process involves a number of pathologic mechanisms, including cell death and inflammation. This review focuses on the role of the c-Jun amino terminal kinase (JNK) signaling pathway in the development of renal fibrosis. The JNK pathway is activated in response to various cellular stresses and plays an important role in cell death and inflammation. Activation of JNK signaling is a common feature in most forms of human kidney injury, evident in both intrinsic glomerular and tubular cells as well as in infiltrating leukocytes...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29113242/eupatolide-inhibits-the-tgf-%C3%AE-1-induced-migration-of-breast-cancer-cells-via-downregulation-of-smad3-phosphorylation-and-transcriptional-repression-of-alk5
#13
Ariundavaa Boldbaatar, Sunyi Lee, Sora Han, Ae Lee Jeong, Hye In Ka, Sumiyasuren Buyanravjikh, Jeong Hyung Lee, Jong-Seok Lim, Myung Sok Lee, Young Yang
The epithelial-mesenchymal transition (EMT) is a hallmark of cancer metastasis, and the associated molecular signaling pathways are regarded as therapeutic targets for cancer treatment. Thus, suppressing EMT with a natural chemical compound may be of therapeutic benefit. Eupatolide is a natural chemical compound extracted from the medicinal plant Inula britannica, which is used in Eastern Asia to treat bronchitis, disorders of the digestive system and inflammation. Besides the anti-inflammatory function of eupatolide, the present study found that eupatolide suppressed the migration and invasion of breast cancer cells, which was associated with the downregulation of vimentin in MDA-MB-231 cells and the upregulation of E-cadherin in MCF-7 cells...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29113082/tgf-%C3%AE-1-smad3-signaling-pathway-mediates-t-2-toxin-induced-decrease-of-type-ii-collagen-in-cultured-rat-chondrocytes
#14
Yang Li, Ning Zou, Jing Wang, Ke-Wei Wang, Fu-Yuan Li, Fu-Xun Chen, Bing-Yu Sun, Dian-Jun Sun
T-2 toxin can cause damage to the articular cartilage, but the molecular mechanism remains unclear. By employing the culture of rat chondrocytes, we investigated the effect of the TGF-β1/Smad3 signaling pathway on the damage to chondrocytes induced by T-2 toxin. It was found that T-2 toxin could reduce cell viability and increased the number of apoptotic cells when compared with the control group. After the addition of the T-2 toxin, the production of type II collagen was reduced at mRNA and protein levels, while the levels of TGF-β1, Smad3, ALK5, and MMP13 were upregulated...
November 5, 2017: Toxins
https://www.readbyqxmd.com/read/29109834/mechanism-of-mechanical-trauma-induced-extracellular-matrix-remodeling-of-fibroblasts-in-association-with-nrf2-are-signaling-suppression-mediating-tgf-%C3%AE-1-smad3-signaling-inhibition
#15
Jianming Tang, Bingshu Li, Cheng Liu, Yang Li, Qiannan Li, Linlin Wang, Jie Min, Ming Hu, Shasha Hong, Li Hong
Stress urinary incontinence (SUI) is a common hygienic problem affecting the quality of women's life worldwide. In this research, we revealed the involvement and regulation of extracellular matrix (ECM) remodeling, oxidative damage, and TGF-β1 signaling in the pathological mechanisms of mechanical trauma-induced SUI. We found that excessive mechanical strain significantly increased apoptosis rate, decreased cell viability and ECM production, and broke the balance of MMPs/TIMPs compared with the nonstrain control (NC) group...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29109401/smad3-initiates-oxidative-stress-and-proteolysis-that-underlies-diaphragm-dysfunction-during-mechanical-ventilation
#16
Huibin Tang, Catherine L Kennedy, Myung Lee, Yang Gao, Hui Xia, Francesca Olguin, Danielle A Fraga, Kelsey Ayers, Sehoon Choi, Michael Kim, Amir Tehrani, Yasser A Sowb, Thomas A Rando, Joseph B Shrager
Prolonged use of mechanical ventilation (MV) leads to atrophy and dysfunction of the major inspiratory muscle, the diaphragm, contributing to ventilator dependence. Numerous studies have shown that proteolysis and oxidative stress are among the major effectors of ventilator-induced diaphragm muscle dysfunction (VIDD), but the upstream initiator(s) of this process remain to be elucidated. We report here that periodic diaphragm contraction via phrenic nerve stimulation (PNS) substantially reduces MV-induced proteolytic activity and oxidative stress in the diaphragm...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29104873/ginsenoside-rg1-attenuates-cigarette-smoke-induced-pulmonary-epithelial-mesenchymal-transition-via-inhibition-of-the-tgf-%C3%AE-1-smad-pathway
#17
Sibin Guan, Weiguo Xu, Fengfeng Han, Wen Gu, Lin Song, Wenjing Ye, Qian Liu, Xuejun Guo
Epithelial-mesenchymal transition (EMT) is a process associated with airway remodeling in chronic obstructive pulmonary disease (COPD), which leads to progressive pulmonary destruction. Panax ginseng is a traditional herbal medicine that has been shown to improve pulmonary function and exercise capacity in patients with COPD. Ginsenoside Rg1 is one of the main active components and was shown to inhibit oxidative stress and inflammation. The present study investigated the hypothesis that ginsenoside Rg1 attenuates EMT in COPD rats induced by cigarette smoke (CS) and human bronchial epithelial (HBE) cells exposed to cigarette smoke extract (CSE)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29102631/edaravone-attenuates-lipopolysaccharide-induced-acute-respiratory-distress-syndrome-associated-early-pulmonary-fibrosis-via-inhibition-of-oxidative-stress-and-transforming-growth-factor-%C3%AE-1-smad3-signaling
#18
Xida Wang, Rongde Lai, Xiangfen Su, Guibin Chen, Zijing Liang
Pulmonary fibrosis is responsible for the both short-term and long-term outcomes in patients with acute respiratory distress syndrome (ARDS). There is still no effective cure to improve prognosis. The purpose of this study was to investigate whether edaravone, a free radical scavenger, have anti-fibrosis effects in the rat model of ARDS associated early pulmonary fibrosis by lipopolysaccharide (LPS) administration. Rats were subjected to intravenous injection of LPS, and edaravone was given intraperitoneally after LPS administration daily for 7 consecutive days...
November 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29102563/tgf-%C3%AE-mediates-renal-fibrosis-via-the-smad3-erbb4-ir-long-noncoding-rna-axis
#19
Min Feng, Patrick Ming-Kuen Tang, Xiao-Ru Huang, Si-Fan Sun, Yong-Ke You, Jun Xiao, Lin-Li Lv, An-Ping Xu, Hui-Yao Lan
Transforming growth factor β (TGF-β)/Smad3 signaling plays a role in tissue fibrosis. We report here that Erbb4-IR is a novel long non-coding RNA (lncRNA) responsible for TGF-β/Smad3-mediated renal fibrosis and is a specific therapeutic target for chronic kidney disease. Erbb4-IR was induced by TGF-β1 via a Smad3-dependent mechanism and was highly upregulated in the fibrotic kidney of mouse unilateral ureteral obstructive nephropathy (UUO). Silencing Erbb4-IR blocked TGF-β1-induced collagen I and alpha-smooth muscle actin (α-SMA) expressions in vitro and effectively attenuated renal fibrosis in the UUO kidney by blocking TGF-β/Smad3 signaling...
October 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29098831/-effect-of-dracocephalum-moldavica-total-flavones-on-expression-of-tgf-%C3%AE-1-smad-signaling-pathway-and-matrix-metalloproteinase-of-atherosclerosis-apoe-mice
#20
Yang Liu, Yi-Ning Quan, Xin-Chun Wang, Xin-Hong Guo, Yong Yuan, Wen-Jiang Cao, Jiang Cheng
To investigate the effect and mechanism of Dracocephalum moldovica total flavones (TFDM) on the formation of atherosclerosis ApoE-/- mice induced by high fat diet. A total of 40 SPF 8-week-old male ApoE-/- mice were fed with high fat diet and randomly divided into 5 groups. TFDM high, medium, low-dose group were given 21, 42, 84 mg•kg⁻¹•d⁻¹ by gavage; Simvastatin group was fed with simvastatin 3.5 mg•kg⁻¹•d⁻¹; and model group was given the same dose of normal saline. The other eight male C57BL/6J mice of the same genetic background and age were set up as control group and fed with common diet...
July 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
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