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https://www.readbyqxmd.com/read/28817807/mir-21-promotes-cardiac-fibrosis-after-myocardial-infarction-via-targeting-smad7
#1
Jinxia Yuan, Hongtao Chen, Dawei Ge, Yu Xu, Haihua Xu, Yang Yang, Ming Gu, Yuhe Zhou, Jingdong Zhu, Ting Ge, Qun Chen, Yue Gao, Yanqing Wang, Xiaowei Li, Yanfang Zhao
BACKGROUND/AIMS: Cardiac fibrosis after myocardial infarction (MI) has been identified as an important factor in the deterioration of heart function. Previous studies have demonstrated that miR-21 plays an important role in various pathophysiological processes in the heart. However, the role of miR-21 in fibrosis regulation after MI remains unclear. METHODS: To induce cardiac infarction, the left anterior descending coronary artery was permanently ligated of mice...
August 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28814088/cisplatin-plus-norcantharidin-alter-the-expression-of-tgf-%C3%AE-1-smads-signaling-pathway-in-hepatocellular-carcinoma
#2
K Y Li, C X Shi, J Z Huang, K L Tang
PURPOSE: To investigate the effects of cisplatin plus norcantharidin on transforming growth factor (TGF)-β1/Smads signaling pathway in hepatocellular carcinoma cells. METHODS: Hepatocellular carcinoma cells (Hep3B) were divided into four groups: control group, cisplatin 2.0 μg/ml group, norcantharidin 10 μg/ml group, and cisplatin 2.0 μg/ml plus norcantharidin 10 μg/ml group. All cells were incubated for 24 hours. Cells proliferation was assessed using cell counting kit-8...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/28810621/effect-of-isopsoralen-on-smad7-in-osteoblastic-mc3t3-e1-cells
#3
Huicun Zhang, Na Ta
The primary pathological change in postmenopausal osteoporosis (PM-OP) is bone collagen loss caused by estrogen depletion. Osteoblasts synthesize type I collagen, which composes the organic matrix of bone. Although isopsoralen stimulates osteoblastic cell proliferation and differentiation, transforming growth factor (TGF)-β1 is an important cell signaling factor for stimulating collagen synthesis. To explore the association between isopsoralen and the synthesis of collagen in vitro, the molecular and biological association between isopsoralen and TGF-β signaling was examined...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28809518/mir-542-promotes-mitochondrial-dysfunction-and-smad-activity-and-is-raised-in-icu-acquired-weakness
#4
Roser Farre Garros, Richard Paul, Martin Connolly, Amy Lewis, Benjamin E Garfield, S Amanda Natanek, Susannah Bloch, Vincent Mouly, Mark J Griffiths, Michael I Polkey, Paul R Kemp
RATIONALE: Loss of skeletal muscle mass and function is a common consequence of critical illness and a range of chronic diseases but the mechanisms by which this occurs are unclear. OBJECTIVES: We aimed to identify miRNAs that were increased in the quadriceps of patients with muscle wasting and to determine the molecular pathways by which they contributed to muscle dysfunction. METHODS: miR-542-3p/-5p were quantified in the quadriceps of patients with COPD and intensive care unit acquired weakness (ICUAW)...
August 15, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28808068/deletion-of-angiotensin-converting-enzyme-2-promotes-hypertensive-nephropathy-by-targeting-smad7-for-ubiquitin-degradation
#5
Zhen Liu, Xiao-Ru Huang, Hai-Yong Chen, Erik Fung, Jian Liu, Hui-Yao Lan
Angiotensin-converting enzyme-2 (ACE2) is downregulated in hypertensive nephropathy. The present study investigated the mechanisms whereby loss of ACE2 promoted angiotensin II-induced hypertensive nephropathy in ACE2 gene knockout mice. We found that compared with wild-type animals, mice lacking ACE2 developed much more severe hypertensive nephropathy in response to chronic angiotensin II infusion, including higher levels of blood pressure, urinary protein excretion, serum creatinine, and progressive renal fibrosis and inflammation...
August 14, 2017: Hypertension
https://www.readbyqxmd.com/read/28807595/sphingosine-kinase-2-deficiency-ameliorates-kidney-fibrosis-by-up-regulating-smad7-in-a-mouse-model-of-unilateral-ureteral-obstruction
#6
Stephanie Schwalm, Sandra Beyer, Helena Frey, Riad Haceni, Georgios Grammatikos, Dominique Thomas, Gerd Geisslinger, Liliana Schaefer, Andrea Huwiler, Josef Pfeilschifter
Kidney fibrosis is a hallmark of chronic kidney disease and leads to extracellular matrix accumulation, organ scarring, and loss of kidney function. In this study, we investigated the role of sphingosine kinase-2 (SPHK2) on the progression of tubular fibrosis by utilizing a mouse unilateral ureteral obstruction (UUO) model. We found that SPHK2 protein and activity are up-regulated in fibrotic renal tissue. Functionally, Sphk2 deficient (Sphk2(-/-)) mice showed an attenuated fibrotic response to UUO compared to wild-type mice as demonstrated by reduced collagen abundance and decreased expression of fibronectin-1, collagen I, α-smooth muscle actin, connective tissue growth factor (CTGF), and plasminogen activator inhibitor (PAI-1)...
August 11, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28801277/-pioglitazone-ameliorates-atherosclerosis-in-apoe-knockout-mice-through-transforming-growth-factor-%C3%AE-smad-signaling-and-adaptive-t-cell-immunity
#7
Yu-Ling Tian, Li-Jun Wang, Yue Wu, Wei-Ping Zhang, Xiao Liang, Zu-Yi Yuan
OBJECTIVE: To examine whether transforming growth factor-β (TGF-β) pathway and adaptive T cell immunity play roles in the anti-atherosclerotic effects of pioglitazone (PIO) in ApoE(-/-) mice. METHODS: ApoE(-/-) mice with atherosclerosis induced by high-fat feeding were treated daily with PIO (20 mg/kg) or vehicle for 8 weeks. The protein expressions of TGF-β pathway in the atheromatous lesions of the aorta and the percentages of IFN-γ(+) and Foxp3(+) cells in the spleen of the mice were examined with immunohistochemical staining...
August 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28769921/microrna-181-variants-regulate-t-cell-phenotype-in-the-context-of-autoimmune-neuroinflammation
#8
Samira Ghorbani, Farideh Talebi, Wing Fuk Chan, Farimah Masoumi, Mohammed Vojgani, Christopher Power, Farshid Noorbakhsh
BACKGROUND: Recent studies have revealed that multiple sclerosis (MS) lesions have distinct microRNA (miRNA) expression profiles. miR-181 family members show altered expression in MS tissues although their participation in MS pathogenesis remains uncertain. Herein, we investigated the involvement of miR-181a and miR-181b in the pathogenesis of MS and its animal model, experimental autoimmune encephalomyelitis (EAE). METHODS: miR-181a and -b levels were measured in the central nervous system (CNS) of patients with MS and mice with EAE as well as relevant leukocyte cultures by real-time RT-PCR...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28764781/effects-of-the-combined-extracts-of-herba-epimedii-and-fructus-ligustrilucidi-on-airway-remodeling-in-the-asthmatic-rats-with-the-treatment-of-budesonide
#9
Xiufeng Tang, Honglei Nian, Xiaoxi Li, Yan Yang, Xiujuan Wang, Liping Xu, Haotian Shi, Xinwei Yang, Renhui Liu
BACKGROUND: Asthma is characterized by chronic airway inflammation, leading to structura1 changes in the airway, collectively termed airway remodeling. Airway remodeling is thought to contribute to airway hyper responsiveness and irreversible airflow limitation. The combination of Herba Epimedii (HE) and Fructus Ligustri Lucidi (FLL) decoction and the systemic administration of glucocorticoids (GC) had a synergistic inhibitory action on airway inflammation in the asthmatic model rats...
August 1, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28734833/transforming-growth-factor-beta-promotes-liver-tumorigenesis-in-mice-via-upregulation-of-snail
#10
Hyuk Moon, Hye-Lim Ju, Sook In Chung, Kyung Joo Cho, Jung Woo Eun, Suk Woo Nam, Kwang-Hyub Han, Diego F Calvisi, Simon Weonsang Ro
BACKGROUND & AIMS: Transforming growth factor beta (TGFB) suppresses early stages of tumorigenesis, but also contributes to migration and metastasis of cancer cells. A large number of human tumors contain mutations that inactivate its receptors, or downstream proteins such as Smad transcription factors, indicating that the TGFB signaling pathway prevents tumor growth. We investigated the effects of TGFB inhibition on liver tumorigenesis in mice. METHODS: C57BL/6 mice received hydrodynamic tail injections of transposons encoding HRAS(G12V) and a short hairpin RNA (shRNA) to downregulate p53, or those encoding HRAS(G12V) and MYC, or those encoding HRAS(G12V) and TAZ(S89), to induce liver tumor formation; mice were also given injections of transposons encoding SMAD7 or shRNA against SMAD2, SMAD3, SMAD4, or SNAI1 (Snail), with or without ectopic expression of Snail...
July 19, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28732737/microrna-181a-and-its-target-smad-7-as-potential-biomarkers-for-tracking-child-acute-lymphoblastic-leukemia
#11
Marwa Nabhan, Manal L Louka, Eman Khairy, Fathy Tash, Randa Ali-Labib, Safinaz El-Habashy
Acute lymphoblastic leukemia (ALL) is the most common pediatric hematologic tumor. MiR-181a was expected to have a role in the development of hematological malignancies; it might act as tumor suppressor or oncogene. Smad7 was selected as miR-181a target pair. It is a negative regulator for the TGF-β1 signaling pathway. In this study, relative expression levels of miR-181a by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), both Smad 7 and TGF β1 proteins levels by enzyme linked immunosorbent assay (ELISA) were all measured in serum of 60 child, 30 with ALL and 30 age and sex matched healthy child as control group...
July 18, 2017: Gene
https://www.readbyqxmd.com/read/28731181/mir%C3%A2-21-promotes-%C3%AE-%C3%A2-sma-and-collagen-i-expression-in-hepatic-stellate-cells-via-the-smad7-signaling-pathway
#12
Rong-Quan Fu, Dan-Ping Hu, Yi-Bing Hu, Liang Hong, Qing-Feng Sun, Ji-Guang Ding
The aim of the present study was to investigate the role of microRNA (miR)‑21 in regulating collagen I and Smad7 expression in activated rat hepatic stellate cells (HSCs). Rat HSCs were isolated by single‑step density gradient centrifugation with Nycodenz. Cellular content of miR‑21, SMAD7, α‑smooth muscle actin (α‑SMA), collagen type I alpha 1 (COLLA1) and COLL alpha 2 (A2) mRNA was examined by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), and cellular content of Smad7 and α‑SMA protein was detected by western blotting...
July 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713920/low%C3%A2-dose-halofuginone-inhibits-the-synthesis-of-type-i-collagen-without-influencing-type-ii-collagen-in-the-extracellular-matrix-of-chondrocytes
#13
Zeng Li, Hao Fei, Zhen Wang, Tianyi Zhu
Full‑thickness and large area defects of articular cartilage are unable to completely repair themselves and require surgical intervention, including microfracture, autologous or allogeneic osteochondral grafts, and autologous chondrocyte implantation. A large proportion of regenerative cartilage exists as fibrocartilage, which is unable to withstand impacts in the same way as native hyaline cartilage, owing to excess synthesis of type I collagen in the matrix. The present study demonstrated that low‑dose halofuginone (HF), a plant alkaloid isolated from Dichroa febrifuga, may inhibit the synthesis of type I collagen without influencing type II collagen in the extracellular matrix of chondrocytes...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28711286/novel-therapeutic-targets-for-inflammatory-bowel-disease
#14
REVIEW
Marjorie Argollo, Gionata Fiorino, Pieter Hindryck, Laurent Peyrin-Biroulet, Silvio Danese
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and Ulcerative Colitis (UC), are immune mediated conditions associated with progressive damage of the inflamed gut tissue, and have a considerable impact on the patient's quality of life. The pathogenesis remains uncertain, but it is clear that complex mechanisms associated with host and luminal factors are involved, generating an unbalance between pro- and anti-inflammatory signaling. It is well established that the purpose of an adequate and complete control of the intestinal inflammation measured not only by clinical symptoms, but also with more objective data such as fecal biomarkers (calprotectin) and endoscopy...
July 12, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28706418/naringenin-prevents-experimental-liver-fibrosis-by-blocking-tgf%C3%AE-smad3-and-jnk-smad3-pathways
#15
Erika Hernández-Aquino, Natanael Zarco, Sael Casas-Grajales, Erika Ramos-Tovar, Rosa E Flores-Beltrán, Jonathan Arauz, Mineko Shibayama, Liliana Favari, Víctor Tsutsumi, José Segovia, Pablo Muriel
AIM: To study the molecular mechanisms involved in the hepatoprotective effects of naringenin (NAR) on carbon tetrachloride (CCl4)-induced liver fibrosis. METHODS: Thirty-two male Wistar rats (120-150 g) were randomly divided into four groups: (1) a control group (n = 8) that received 0.7% carboxy methyl-cellulose (NAR vehicle) 1 mL/daily p.o.; (2) a CCl4 group (n = 8) that received 400 mg of CCl4/kg body weight i.p. 3 times a week for 8 wk; (3) a CCl4 + NAR (n = 8) group that received 400 mg of CCl4/kg body weight i...
June 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28698735/cardioprotection-against-heart-failure-by-shenfu-injection-via-tgf-%C3%AE-smads-signaling-pathway
#16
Jingyu Ni, Yang Shi, Lan Li, Jingrui Chen, Lingyan Li, Min Li, Jinqiang Zhu, Yan Zhu, Guanwei Fan
OBJECTIVE: To explore the potential cardioprotective mechanism of Shenfu injection (SFI) against heart failure (HF) by attenuating myocardial fibrosis and cardiac remodeling. METHODS AND RESULTS: Four weeks after myocardial infarction (MI), adult male Sprague Dawley rats were randomized for 4-week treatment with Valsartan, SFI, or vehicle. Echocardiography and hemodynamics were applied to evaluate cardiac functions. Myocardia of coronary artery ligated (CAD) rats were observed to investigate changes in cardiac structure and function...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28690543/frontiers-in-drug-research-and-development-for-inflammatory-bowel-disease
#17
REVIEW
Diego Currò, Daniela Pugliese, Alessandro Armuzzi
Inflammatory bowel disease (IBD) is idiopathic, lifelong, immune-mediated diseases, for which curative therapies are not yet available. In the last 15 years, the introduction of monoclonal antibodies targeting tumor necrosis factor-α, a cytokine playing a key role in bowel inflammation, has revolutionized treatment paradigms for IBD. Despite their proven long-term efficacy, however, many patients do not respond or progressively lose response to these drugs. Major advances of knowledge in immunology and pathophysiology of intestinal inflammatory processes have made possible the identification of new molecular targets for drugs, thus opening several new potential therapeutic opportunities for IBD...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28685927/altering-equine-corneal-fibroblast-differentiation-through-smad-gene-transfer
#18
Todd L Marlo, Elizabeth A Giuliano, Ratnakar Tripathi, Ajay Sharma, Rajiv R Mohan
OBJECTIVE: To explore the impact of equine corneal fibroblast (ECF) to myofibroblast (ECM) differentiation by altering the expression of the Smad genes either individually or in combination. Specifically, we sought to examine the ECF differentiation after (a) silencing of Smad2, 3, and 4 profibrotic genes individually and (b) overexpression of antifibrotic Smad7 gene and in a combination with pro- and antifibrotic Smad genes. METHODS: Equine corneal fibroblast primary cultures were generated as previously described...
July 6, 2017: Veterinary Ophthalmology
https://www.readbyqxmd.com/read/28676447/profiling-conserved-biological-pathways-in-autosomal-dominant-polycystic-kidney-disorder-adpkd-to-elucidate-key-transcriptomic-alterations-regulating-cystogenesis-a-cross-species-meta-analysis-approach
#19
REVIEW
Shatakshee Chatterjee, Srikant Prasad Verma, Priyanka Pandey
PURPOSE: Initiation and progression of fluid filled cysts mark Autosomal Dominant Polycystic Kidney Disease (ADPKD). Thus, improved therapeutics targeting cystogenesis remains a constant challenge. Microarray studies in single ADPKD animal models species with limited sample sizes tend to provide scattered views on underlying ADPKD pathogenesis. Thus we aim to perform a cross species meta-analysis to profile conserved biological pathways that might be key targets for therapy. METHODS: Nine ADPKD microarray datasets on rat, mice and human fulfilled our study criteria and were chosen...
September 5, 2017: Gene
https://www.readbyqxmd.com/read/28674186/tgf%C3%AE-nr4a1-inducible-breast-cancer-cell-migration-and-epithelial-to-mesenchymal-transition-is-p38%C3%AE-mapk14-dependent
#20
Erik Hedrick, Stephen Safe
Transforming growth factor β (TGFβ)-induced migration of triple negative breast cancer (TNBC) cells is dependent on nuclear export of the orphan receptor NR4A1 which plays a role in proteasome-dependent degradation of SMAD7. In this study, we show that TGFβ induces p38α (MAPK14) which in turn phosphorylates NR4A1, resulting in nuclear export of the receptor. TGFβ/p38α and NR4A1 also play essential roles in the induction of epithelial to mesenchymal transition (EMT) and induction of β-catenin in TNBC cells, and these TGFβ-induced responses and nuclear export of NR4A1 are blocked by NR4A1 antagonists, the p38 inhibitor SB202190, kinase dead [p38(KD)] and dominant negative [p38(DN)] forms of p38α...
July 3, 2017: Molecular and Cellular Biology
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