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https://www.readbyqxmd.com/read/28805484/disparate-phospho-smad2-levels-in-advanced-type-2-diabetes-patients-with-diabetic-nephropathy-and-early-experimental-db-db-mouse-model
#1
Lise Høj Thomsen, Morten Fog-Tonnesen, Lisbeth Nielsen Fink, Jenny Norlin, Amaya García de Vinuesa, Troels Krarup Hansen, Emile de Heer, Peter Ten Dijke, Alexander Rosendahl
Uncontrolled activation of transforming growth factor beta (TGF-β) family members is hypothesized to participate in type 2 diabetes (T2D) dependent diabetic nephropathy (DN). We evaluated and compared downstream activation of the Smad2-signaling pathway in kidney samples from T2D patients to kidneys from the T2D model of leptin receptor deficient db/db mouse. Furthermore, expression of TGF-β family members was evaluated to elucidate molecular mechanisms in the mouse model. Kidney samples from patients with advanced stages of DN showed elevated pSmad2 staining whereas db/db mouse kidneys surprisingly showed a decrease in pSmad2 in the tubular compartment...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28804566/microrna-93-inhibits-apoptosis-and-promotes-proliferation-invasion-and-migration-of-renal-cell-carcinoma-achn-cells-via-the-tgf-%C3%AE-smad-signaling-pathway-by-targeting-runx3
#2
Li-Jie Liu, Jian-Jun Yu, Xiao-Lin Xu
We investigated the ability of microRNA-93 (miR-93) to influence proliferation, invasion, migration, and apoptosisofrenal cell carcinoma (RCC) cells via transforming growth factor-β/solvated metal atom dispersed (TGF-β/Smad) signaling by targeting runt-related transcription factor 3 (RUNX3). RCC tissues with corresponding adjacent normal tissues were collected from 249 RCC patients. And normal renal tissues were collected from patients without RCC who received nephrectomy. The RCC cell line ACHN was treated with miR-93 mimic, mimic-negative control (NC), miR-93 inhibitor, inhibitor-NC, and miR-93 inhibitor + small interfering RNA (siRNA) against RUNX3 (si-RUNX3)...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28803990/high-doses-of-baicalin-induces-kidney-injury-and-fibrosis-through-regulating-tgf-%C3%AE-smad-signaling-pathway
#3
Yi Cai, Wanqing Ma, Yichuan Xiao, Bo Wu, Xiaobing Li, Fengrong Liu, Jianhua Qiu, Genshui Zhang
Baicalin is a major flavonoid compound purified from Scutellariae radix, which has been described as an herb in the Chinese Pharmacopoeia. Previous studies have suggested baicalin possessed extensive anti-inflammatory, anti-cancer, anti-viral properties. However, up to known, there have been no reports of safety and toxicity in the rats following oral administration of baicalin. In this present study, we showed the first evidence that treatment of baicalin (400, 800 and 1600mg/kg/day) induced significantly kidney injury and fibrosis...
August 10, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28803964/tgf%C3%AE-smad-signalling-modulates-mll-and-mll-af4-mediated-5-lipoxygenase-promoter-activation
#4
Meike J Saul, Florian Groher, Anett B Hegewald, Michaela Müller-McNicoll, Rolf Marschalek, Beatrix Suess, Dieter Steinhilber
5-Lipoxygenase (5-LO) catalyzes the initial two steps of the conversion of arachidonic acid to leukotrienes which represent a group of pro-inflammatory lipid mediators involved in immune defense reactions as well as inflammation, allergy and cancer. Transforming growth factor-β (TGFβ) and calcitriol strongly upregulate 5-LO expression during myeloid cell differentiation and MLL-AF4 has been shown to strongly activate the 5-LO promoter. Here, we investigated the role of TGFβ/SMAD signalling in 5-LO promoter activation...
August 10, 2017: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/28801702/paeonol-attenuates-aging-mrc-5-cells-and-inhibits-epithelial-mesenchymal-transition-of-premalignant-hacat-cells-induced-by-aging-mrc-5-cell-conditioned-medium
#5
Lihua Yang, Shangping Xing, Kun Wang, Hua Yi, Biaoyan Du
Senescence-associated secretory phenotype (SASP) factors, such as IL-6 and IL-8, are extremely critical in tissue microenvironment. Senescent human fibroblasts facilitate epithelial-mesenchymal transition (EMT) in premalignant epithelial cells mainly through the secretion of SASP factors. Meanwhile, premalignant human HaCaT Keratinocyte (HaCaT) cells as immortal epithelial cells are susceptible to malignant transformation. Paeonol, an herbal phenolic component found in peonies, exerts anti-aging and anti-tumor efficacies, while the molecular mechanisms of paeonol on EMT in premalignant HaCaT cells induced by SASP factors are unclear...
August 12, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28801455/correction-for-chen-et-al-nuclear-export-of-smads-by-ranbp3l-regulates-bone-morphogenetic-protein-signaling-and-mesenchymal-stem-cell-differentiation
#6
Fenfang Chen, Xia Lin, Pinglong Xu, Zhengmao Zhang, Yanzhen Chen, Chao Wang, Jiahuai Han, Bin Zhao, Mu Xiao, Xin-Hua Feng
No abstract text is available yet for this article.
September 1, 2017: Molecular and Cellular Biology
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/28799829/radiotherapy-induces-cell-cycle-arrest-and-cell-apoptosis-in-nasopharyngeal-carcinoma-via-the-atm-and-smad-pathways
#8
Ming-Yi Li, Jin-Quan Liu, Dong-Ping Chen, Zhou-Yu Li, Bin Qi, Lu He, Yi Yu, Wen-Jin Yin, Meng-Yao Wang, Ling Lin
Nasopharyngeal carcinoma (NPC) is a common malignant neoplasm of the head and neck which is harmful to human's health. Radiotherapy is commonly used in the treatment of NPC and it induces immediate cell cycle arrest and cell apoptosis. However, the mechanism remains unknown. Evidences suggested the activation of Ataxia telangiectasia mutated (ATM) pathway and Smad pathway are two of the important crucial mediators in the function of radiotherapy. In this study, we carried out in vitro assays with human nasopharyngeal carcinoma CNE-2 cells and in vivo assays with nude mice to investigate the role of the ATM and Smad pathways in the treatment of nasopharyngeal carcinoma with radiotherapy...
August 11, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28794616/schisandrin-b-attenuates-ccl4-induced-liver-fibrosis-in-rats-by-regulation-of-nrf2-are-and-tgf-%C3%AE-smad-signaling-pathways
#9
Qingshan Chen, Hai Zhang, Yan Cao, Ying Li, Sen Sun, Junping Zhang, Guoqing Zhang
Liver fibrosis is a major pathological feature of chronic liver diseases and there is no effective therapy program at present. Schisandrin B (Sch B) is the major bioactive ingredient of Schisandra chinensis, with antioxidative, anti-inflammatory, antitumor, and hepatoprotective properties. This study aimed to investigate the protective effect and related molecular mechanism of Sch B against carbon tetrachloride (CCl4)-induced liver fibrosis in rats. The in vivo therapeutic effect of Sch B on liver fibrosis induced by CCl4 was examined in rats...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28791366/juglone-reduces-growth-and-migration-of-u251-glioblastoma-cells-and-disrupts-angiogenesis
#10
Jian Wang, Ke Liu, Xiao-Feng Wang, Dian-Jun Sun
Accumulating data show that prolylisomerase (Pin1) is overexpressed in human glioblastoma multiforme (GBM) specimens. Therefore, Pin1 inhibitors should be investigated as a new chemotherapeutic drug that may enhance the clinical management of human gliomas. Recently, juglone, a Pin1 inhibitor, was shown to exhibit potent anticancer activity in various tumor cells, but its role in human glioma cells remains unknown. In the present study, we determined if juglone exerts antitumor effects in the U251 human glioma cell line and investigated its potential underlying molecular mechanisms...
August 3, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28790434/regulation-of-osteoclast-differentiation-by-myosin-x
#11
Amy Tasca, Kristina Astleford, Ari Lederman, Eric D Jensen, Beth S Lee, Rajaram Gopalakrishnan, Kim C Mansky
Osteoclasts begin as mononuclear cells that fuse to form multinuclear cells able to resorb bone. The mechanisms that regulate all the steps of osteoclast differentiation are not entirely known. MYO10, an unconventional myosin, has previously been shown in mature osteoclasts to play a role in attachment and podosome positioning. We determined that MYO10 is also expressed early during osteoclast differentiation. Loss of MYO10 expression in osteoclast precursors inhibits the ability of mononuclear osteoclasts to fuse into multinuclear osteoclasts...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28790310/p16-ink4a-deletion-ameliorated-renal-tubulointerstitial-injury-in-a-stress-induced-premature-senescence-model-of-bmi-1-deficiency
#12
Jianliang Jin, Jianguo Tao, Xin Gu, Zhenzhen Yu, Rong Wang, Guoping Zuo, Qing Li, Xianhui Lv, Dengshun Miao
To determine whether p16 (INK4a) deletion ameliorated renal tubulointerstitial injury by inhibiting a senescence-associated secretory phenotype (SASP) in Bmi-1-deficient (Bmi-1 (-/-)) mice, renal phenotypes were compared among 5-week-old Bmi-1 and p16 (INK4a) double-knockout, and Bmi-1 (-/-) and wild-type mice. Fifth-passage renal interstitial fibroblasts (RIFs) from the three groups were analyzed for senescence and proliferation. The effect of Bmi-1 deficiency on epithelial-to-mesenchymal transition (EMT) was examined in Bmi-1-knockdown human renal proximal tubular epithelial (HK2) cells, which were treated with concentrated conditioned medium (CM) from the fifth-passage renal interstitial fibroblasts (RIFs) of above three group mice or with exogenous TGF-β1...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28789951/hepatoprotective-activities-of-rosmarinic-acid-against-extrahepatic-cholestasis-in-rats
#13
Shih-Yi Lin, Ya-Yu Wang, Wen-Ying Chen, Su-Lan Liao, Su-Tze Chou, Ching-Ping Yang, Chun-Jung Chen
Though rosmarinic acid possesses nutritional, pharmaceutical, and toxic properties and shows therapeutic potential on liver diseases, its therapeutic effects against cholestatic liver diseases have not been proven. Using an extrahepatic cholestasis rat model by bile-duct ligation (BDL), daily oral administration of rosmarinic acid showed improvement effects on liver histology, serum biochemicals, ductular reaction, oxidative stress, inflammation, and fibrosis. Rosmarinic acid alleviated BDL-induced transforming growth factor beta-1 (TGF-β1) production and hepatic collagen deposition, and the anti-fibrotic effects were accompanied by reductions in matrix-producing cells and Smad2/3...
August 5, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28783176/short-stretches-of-rare-codons-regulate-translation-of-the-transcription-factor-zeb2-in-cancer-cells
#14
W R Wan Makhtar, G Browne, A Karountzos, C Stevens, Y Alghamdi, A R Bottrill, S Mistry, E Smith, M Bushel, J H Pringle, A E Sayan, E Tulchinsky
Two proteins comprising the ZEB family of zinc finger transcription factors, ZEB1 and ZEB2, execute EMT programs in embryonic development and cancer. By studying regulation of their expression, we describe a novel mechanism that limits ZEB2 protein synthesis. A protein motif located at the border of the SMAD-binding domain of ZEB2 protein induces ribosomal pausing and compromises protein synthesis. The function of this protein motif is dependent on stretches of rare codons, Leu(UUA)-Gly(GGU)-Val(GUA). Incorporation of these triplets in the homologous region of ZEB1 does not affect protein translation...
August 7, 2017: Oncogene
https://www.readbyqxmd.com/read/28783105/viral-ubiquitin-ligase-stimulates-selective-host-microrna-expression-by-targeting-zeb-transcriptional-repressors
#15
Gabriel Lutz, Igor Jurak, Eui Tae Kim, Ju Youn Kim, Michael Hackenberg, Andrew Leader, Michelle L Stoller, Donna M Fekete, Matthew D Weitzman, Donald M Coen, Angus C Wilson
Infection with herpes simplex virus-1 (HSV-1) brings numerous changes in cellular gene expression. Levels of most host mRNAs are reduced, limiting synthesis of host proteins, especially those involved in antiviral defenses. The impact of HSV-1 on host microRNAs (miRNAs), an extensive network of short non-coding RNAs that regulate mRNA stability/translation, remains largely unexplored. Here we show that transcription of the miR-183 cluster (miR-183, miR-96, and miR-182) is selectively induced by HSV-1 during productive infection of primary fibroblasts and neurons...
August 7, 2017: Viruses
https://www.readbyqxmd.com/read/28781950/role-of-the-tgf-%C3%AE-pathway-in-dedifferentiation-of-human-mature-adipocytes
#16
Julie Anne Côté, Julie Lessard, Mélissa Pelletier, Simon Marceau, Odette Lescelleur, Julie Fradette, André Tchernof
Dedifferentiation of adipocytes contributes to the generation of a proliferative cell population that could be useful in cellular therapy or tissue engineering. Adipocytes can dedifferentiate into precursor cells to acquire a fibroblast-like phenotype using ceiling culture, in which the buoyancy of fat cells is exploited to allow them to adhere to the inner surface of a container. Ceiling culture is usually performed in flasks, which limits the ability to test various culture conditions. Using a new six-well plate ceiling culture approach, we examined the relevance of TGF-β signaling during dedifferentiation...
August 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28780752/regulation-of-smad-mediated-microrna-transcriptional-response-in-ground-squirrels-during-hibernation
#17
Cheng-Wei Wu, Kenneth B Storey
Mammalian hibernation is a state of dormancy that is used by some animals to survive through the unfavorable conditions of winter, and is characterized by coordinated suppression of basal metabolism that is supported by global inhibition of energy/ATP-consuming processes. In this study, we examine the regulation of the anti-proliferatory TGF-β/Smad transcription factor signaling pathway in the liver tissue of the hibernating 13-lined ground squirrel Ictidomys tridecemlineatus. The TGF-β/Smad signaling pathway is known to mediate cell cycle arrest through induction of cell cycle dependent kinase inhibitors, and more recently, has been shown to regulate a wide range of cellular processes via its control of microRNA biosynthesis...
August 5, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28779848/tgf-%C3%AE-1-stimulates-cyclooxygenase-2-expression-and-pge2-production-of-human-dental-pulp-cells-role-of-alk5-smad2-and-mek-erk-signal-transduction-pathways
#18
Po-Shuen Lin, Ru-Hsiu Cheng, Mei-Chi Chang, Jang-Jaer Lee, Hsiao-Hua Chang, Wei-Ling Huang, Sin-Yuet Yeung, Ya-Ching Chang, Jiiang-Huei Jeng
BACKGROUND/PURPOSES: TGF-β1 is an important growth factor that may influence the odontoblast differentiation and matrix deposition in the reactionary/reparative dentinogenesis to dental caries or other tooth injuries. TGF-β1 exerts its effects through various signaling pathways, such as Smads and MAPKs. Cyclooxygenase-2 (COX-2) is a membrane-associated enzyme that produces prostaglandin E2 (PGE2) at sites of pulpal injury and inflammation, which leads to tissue swelling, redness and pain...
August 2, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28774593/inhibiton-of-fkbp10-attenuates-hypertrophic-scarring-through-suppressing-fibroblast-activity-and-extracellualr-matrix-deposition
#19
Xiao Liang, Bangda Chai, Ran Duan, Yiwen Zhou, Xiaolu Huang, Qingfeng Li
Hypertrophic scar (HS) is a pathogenic form of scar formation with no recognized treatment to date. Its molecular mechanism is related to the abnormal proliferation and transition of fibroblasts and overproduction of extracellular matrix (ECM). FK506-binding protein 10 (FKBP10) is a molecular chaperone able of regulating α-SMA expression and pro-collagen maturation in fibroblasts. However, no research has investigated the biological function of FKBP10 in scar formation to date. In this study, we aim to assess the expression and function of FKBP10 in hypertrophic scarring...
July 31, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28771711/tannic-acid-attenuates-tgf-%C3%AE-1-induced-epithelial-to-mesenchymal-transition-by-effectively-intervening-tgf-%C3%AE-signaling-in-lung-epithelial-cells
#20
Dhamotharan Pattarayan, Ayyanar Sivanantham, Venkateshwaran Krishnaswami, Lakshmanan Loganathan, Rajaguru Palanichamy, Subramanian Natesan, Karthikeyan Muthusamy, Subbiah Rajasekaran
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and an irreversible lung disorder characterized by the accumulation of fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor-β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT) is thought to be one of the possible sources for a substantial increase in the number of fibroblasts/myofibroblasts in IPF lungs. Tannic acid (TA), a natural dietary polyphenolic compound has been shown to possess diverse pharmacological effects...
August 3, 2017: Journal of Cellular Physiology
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