keyword
MENU ▼
Read by QxMD icon Read
search

Alk5 kinase inhibitor

keyword
https://www.readbyqxmd.com/read/29627157/tgfb1-modulates-in-vitro-secretory-activity-and-viability-of-equine-luteal-cells
#1
António Galvão, Karolina Wolodko, Maria Rosa Rebordão, Dariusz Skarzynski, Graça Ferreira-Dias
In the present report we describe the involvement of transforming growth factor B1 (TGF) in functional regression and structural luteolysis in the mare. Firstly, TGF and its receptors activin-like kinase (ALK) 5 and TGF receptor 2 were identified in corpus luteum (CL) steroidogenic, endothelial and fibroblast-like cells. Also, TGF and ALK5 protein expression were shown to be increased in Mid-, and Late-CL (p < 0.05). Subsequently, using an in vitro model with Mid-CL cells, we studied the role of TGF on secretory activity and cell viability...
April 4, 2018: Cytokine
https://www.readbyqxmd.com/read/29514186/cc-401-promotes-%C3%AE-cell-replication-via-pleiotropic-consequences-of-dyrk1a-b-inhibition
#2
Yassan Abdolazimi, Sooyeon Lee, Haixia Xu, Paul Allegretti, Timothy M Horton, Benjamin Yeh, Hannah P Moeller, Robert J Nichols, David McCutcheon, Aryaman Shalizi, Mark Smith, Neali A Armstrong, Justin P Annes
Pharmacologic expansion of endogenous β-cells is a promising therapeutic strategy for diabetes. To elucidate the molecular pathways that control β-cell growth we screened ∼2,400 bioactive compounds for rat β-cell replication-modulating activity. Numerous hit compounds impaired or promoted rat β-cell replication, including CC-401, an advanced clinical candidate previously characterized as a c-Jun N-terminal kinase (JNK) inhibitor. Surprisingly, CC-401 induced rodent (in vitro and in vivo) and human (in vitro) β-cell replication via dual specificity tyrosine-phosphorylation-regulated kinases (DYRK1A/B) inhibition...
March 5, 2018: Endocrinology
https://www.readbyqxmd.com/read/29499695/mekk1-jnk-and-smad3-mediate-cxcl12-stimulated-connective-tissue-growth-factor-expression-in-human-lung-fibroblasts
#3
Chien-Huang Lin, Chung-Huang Shih, Yu-Chang Lin, You-Lan Yang, Bing-Chang Chen
BACKGROUND: In idiopathic pulmonary fibrosis, the interaction of CXCL12 and CXC receptor 4 (CXCR4) plays a critical role in lung fibrosis. Connective tissue growth factor (CTGF) overexpression underlies the development of pulmonary fibrosis. Our previous report showed that the Rac1-dependent extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and activator protein (AP)-1 pathways are involved in CXCL12-generated CTGF expression in human lung fibroblasts (WI-38)...
March 2, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29456135/pericyte-alk5-timp3-axis-contributes-to-endothelial-morphogenesis-in-the-developing-brain
#4
Jui M Dave, Teodelinda Mirabella, Scott D Weatherbee, Daniel M Greif
The murine embryonic blood-brain barrier (BBB) consists of endothelial cells (ECs), pericytes (PCs), and basement membrane. Although PCs are critical for inducing vascular stability, signaling pathways in PCs that regulate EC morphogenesis during BBB development remain unexplored. Herein, we find that murine embryos lacking the transforming growth factor β (TGF-β) receptor activin receptor-like kinase 5 (Alk5) in brain PCs (mutants) develop gross germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH)...
February 8, 2018: Developmental Cell
https://www.readbyqxmd.com/read/29416020/bone-morphogenetic-protein-2-promotes-human-trophoblast-cell-invasion-by-upregulating-n-cadherin-via-non-canonical-smad2-3-signaling
#5
Hong-Jin Zhao, Christian Klausen, Yan Li, Hua Zhu, Yan-Ling Wang, Peter C K Leung
BMP2 expression is spatiotemporally correlated with embryo implantation and is crucial for endometrial decidualization and fertility in mice. BMP2 has been reported to increase the mesenchymal adhesion molecule N-cadherin and enhance cell invasion in cancer cells; moreover, studies suggest that N-cadherin promotes placental trophoblast invasion. However, whether BMP2 can promote trophoblast cell invasion during placentation remains unknown. The objective of our study was to investigate the effects of BMP2 on human trophoblast cell invasion and the involvement of N-cadherin and SMAD signaling...
February 7, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29405089/correction-to-cassidy-et-al-disposition-and-metabolism-of-14c-galunisertib-a-tgf-bri-kinase-alk5-inhibitor-following-oral-administration-in-healthy-subjects-and-mechanistic-prediction-of-the-effect-of-itraconazole-on-galunisertib-pharmacokinetics
#6
https://www.readbyqxmd.com/read/29279601/isolation-and-culture-of-primary-mouse-retinal-pigment-epithelial-rpe-cells-with-rho-kinase-and-tgf%C3%AE-r-1-alk5-inhibitor
#7
Junhui Shen, Jianfeng He, Fang Wang
BACKGROUND Primary RPE cells could be a reliable model for representing in vivo status of RPE compared with cell lines. We present a protocol for in vitro isolation and culture of primary RPE cells from C57BL mice. MATERIAL AND METHODS We used C57BL mice ages 7 days to 4 months. The RPE layer was separated from the neural retina layer by digestion with 2% Dispase for 45 min and scraped off from the choroid after 25-min incubation in 37°C. Collected RPE sheets were gently pipetted up into smaller sheets. RPE sheets were transferred into well plates and cultured in vitro for 2 weeks...
December 27, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29261154/the-role-of-par2-in-tgf-%C3%AE-1-induced-erk-activation-and-cell-motility
#8
Hendrik Ungefroren, David Witte, Christian Fiedler, Thomas Gädeken, Roland Kaufmann, Hendrik Lehnert, Frank Gieseler, Bernhard H Rauch
BACKGROUND: Recently, the expression of proteinase-activated receptor 2 (PAR2) has been shown to be essential for activin receptor-like kinase 5 (ALK5)/SMAD-mediated signaling and cell migration by transforming growth factor (TGF)-β1. However, it is not known whether activation of non-SMAD TGF-β signaling (e.g., RAS-RAF-MEK-extracellular signal-regulated kinase (ERK) signaling) is required for cell migration and whether it is also dependent on PAR2. METHODS: RNA interference was used to deplete cells of PAR2, followed by xCELLigence technology to measure cell migration, phospho-immunoblotting to assess ERK1/2 activation, and co-immunoprecipitation to detect a PAR2-ALK5 physical interaction...
December 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29229918/negative-regulation-of-tgf-%C3%AE-1-induced-mkk6-p38-and-mek-erk-signalling-and-epithelial-mesenchymal-transition-by-rac1b
#9
David Witte, Hannah Otterbein, Maria Förster, Klaudia Giehl, Robert Zeiser, Hendrik Lehnert, Hendrik Ungefroren
Prompted by earlier findings that the Rac1-related isoform Rac1b inhibits transforming growth factor (TGF)-β1-induced canonical Smad signalling, we studied here whether Rac1b also impacts TGF-β1-dependent non-Smad signalling such as the MKK6-p38 and MEK-ERK mitogen-activated protein kinase (MAPK) pathways and epithelial-mesenchymal transition (EMT). Transient depletion of Rac1b protein in pancreatic cancer cells by RNA interference increased the extent and duration of TGF-β1-induced phosphorylation of p38 MAPK in a Smad4-independent manner...
December 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29191563/tgf-%C3%AE-1-p53-signaling-in-renal-fibrogenesis
#10
REVIEW
Stephen P Higgins, Yi Tang, Craig E Higgins, Badar Mian, Wenzheng Zhang, Ralf-Peter Czekay, Rohan Samarakoon, David J Conti, Paul J Higgins
Fibrotic disorders of the renal, pulmonary, cardiac, and hepatic systems are associated with significant morbidity and mortality. Effective therapies to prevent or curtail the advancement to organ failure, however, remain a major clinical challenge. Chronic kidney disease, in particular, constitutes an increasing medical burden affecting >15% of the US population. Regardless of etiology (diabetes, hypertension, ischemia, acute injury, urologic obstruction), persistently elevated TGF-β1 levels are causatively linked to the activation of profibrotic signaling networks and disease progression...
March 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29064324/2d-qsar-study-molecular-docking-and-molecular-dynamics-simulation-studies-of-interaction-mechanism-between-inhibitors-and-transforming-growth-factor-beta-receptori-alk5
#11
Meng-Nan Jiang, Xiao-Ping Zhou, Dong-Ru Sun, Huan Gao, Qing-Chuan Zheng, Hong-Xing Zhang, Di Liang
Transforming growth factor type 1 receptor (ALK5) is kinase associated with a wide variety of pathological processes, and inhibition of ALK5 is a good strategy to treat many kinds of cancer and fibrotic diseases. Recently a series of compounds have been synthesized as ALK5 inhibitors. However, the study of their selectivity against other potential targets remains elusive. In this research, adataset of ALK5 inhibitors were collected and studied based on the combination of 2D-QSAR, molecular docking and molecular dynamics simulation...
October 24, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28969055/mir-338-3p-inhibits-the-invasion-of-renal-cell-carcinoma-by-downregulation-of-alk5
#12
Xiaoqian Zhang, Chunxia Wang, Hui Li, Xiaobin Niu, Xinwei Liu, Dongxu Pei, Xiaolan Guo, Xiaona Xu, Yongwei Li
BACKGROUND: The current study aims to elucidate the role of miRNA-338-3p (miR-338-3p) in the invasion of renal cell carcinoma (RCC). METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to detect the expression of miR-338-3p in human RCC cell lines with high metastatic potential (Caki-1) and low metastatic potential (786-O), respectively. The Caki-1 and 786-O cells were transfected with miR-338-3p mimic or inhibitor. Wound healing assay, Transwell assay and western blotting were performed to analyze the invasive ability and expression of activin receptor-like kinase 5 (ALK5) in the RCC cell lines...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28939526/inhibition-of-the-tgf-%C3%AE-1-smad-signaling-pathway-protects-against-cartilage-injury-and-osteoarthritis-in-a-rat-model
#13
Yong-Jian Wang, Min Shen, Shan Wang, Xin Wen, Xin-Rui Han, Zi-Feng Zhang, Hui Li, Fei Wang, Dong-Mei Wu, Jun Lu, Yuan-Lin Zheng
Transforming growth factor-β1 (TGF-β1) in osteoblastic cells triggers pathological changes observed in osteoarthritis (OA). Thus, we hypothesized that the inhibition of the TGF-β1/Smad signaling pathway could act to protect against cartilage injury in rats with OA. After establishment of rat models induced by papain and L-cysteine, rats were subsequently assigned into the TβRI inhibitors, normal control (NC) and OA model groups. RT-qPCR and western blotting were performed to determine mRNA and protein expressions of TGFβ1, Smad2, Smad3 and Activin receptor-like kinase 5 (ALK5), respectively...
November 15, 2017: Life Sciences
https://www.readbyqxmd.com/read/28815607/a-3d-tri-culture-system-reveals-that-activin-receptor-like-kinase-5-and-connective-tissue-growth-factor-drive-human-glomerulosclerosis
#14
John P Waters, Yvonne C Richards, Jeremy N Skepper, Mark Southwood, Paul D Upton, Nicholas W Morrell, Jordan S Pober, John R Bradley
Glomerular scarring, known as glomerulosclerosis, occurs in many chronic kidney diseases and involves interaction between glomerular endothelial cells (GECs), podocytes, and mesangial cells (MCs), leading to signals that promote extracellular matrix deposition and endothelial cell dysfunction and loss. We describe a 3D tri-culture system to model human glomerulosclerosis. In 3D monoculture, each cell type alters its phenotype in response to TGFβ, which has been implicated as an important mediator of glomerulosclerosis...
November 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28767427/mir-338-3p-inhibits-the-invasion-of-renal-cell-carcinoma-by-downregulation-of-alk5
#15
Xiaoqian Zhang, Chunxia Wang, Hui Li, Xiaobin Niu, Xinwei Liu, Dongxu Pei, Xiaolan Guo, Xiaona Xu, Yongwei Li
BACKGROUND: The current study aims to elucidate the role of miRNA-338-3p (miR-338-3p) in the invasion of renal cell carcinoma (RCC). METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to detect the expression of miR-338-3p in human RCC cell lines with high metastatic potential (Caki-1) and low metastatic potential (786-O), respectively. The Caki-1 and 786-O cells were transfected with miR-338-3p mimic or inhibitor. Wound healing assay, Transwell assay and western blotting were performed to analyze the invasive ability and expression of activin receptor-like kinase 5 (ALK5) in the RCC cell lines...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28694529/the-production-of-fibroblast-growth-factor-23-is-controlled-by-tgf-%C3%AE-2
#16
Martina Feger, Philipp Hase, Bingbing Zhang, Frank Hirche, Philipp Glosse, Florian Lang, Michael Föller
Transforming growth factor-β (TGF-β) is a cytokine produced by many cell types and implicated in cell growth, differentiation, apoptosis, and inflammation. It stimulates store-operated calcium entry (SOCE) through the calcium release-activated calcium (CRAC) channel Orai1/Stim1 in endometrial Ishikawa cells. Bone cells generate fibroblast growth factor (FGF) 23, which inhibits renal phosphate reabsorption and 1,25(OH)2D3 formation in concert with its co-receptor Klotho. Moreover, Klotho and FGF23 counteract aging and age-related clinical conditions...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28632033/overexpression-of-alk5-induces-human-tenon-s-capsule-fibroblasts-transdifferentiation-and-fibrosis-in-vitro
#17
Shu-Hao Fu, Hui-Ying Wang, Jia-Ying Zhang, Hui-Min Shi, Nan Zhang, Wen Ye, Yi-Qin Xiao
PURPOSE: To investigate the involvement of activin receptor-like kinase 5 (ALK5) in human Tenon's capsule fibroblasts (HTFs) transdifferentiation and fibrosis. METHODS: (1) Cultured HTFs were treated with transforming growth factor beta 1 (TGF-β1) at different concentrations for different durations, mRNA expression of ALK5 and plasminogen activator inhibitor-1 (PAI-1) was measured by quantitative polymerase chain reaction (PCR) while protein expression of ALK5, α-smooth muscle actin (α-SMA), and extracellular matrix deposition including fibronectin (FN) and collagen I (Col1) was assessed by western blot...
February 28, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28569204/tgf%C3%AE-1-induced-smad2-3-and-smad1-5-phosphorylation-are-both-alk5-kinase-dependent-in-primary-chondrocytes-and-mediated-by-tak1-kinase-activity
#18
Arjan van Caam, Wojciech Madej, Amaya Garcia de Vinuesa, Marie-José Goumans, Peter Ten Dijke, Esmeralda Blaney Davidson, Peter van der Kraan
BACKGROUND: Dysregulated transforming growth factor β (TGFβ) signaling is implicated in osteoarthritis development, making normalizing TGFβ signaling a possible therapy. Theoretically, this can be achieved with small molecule inhibitors specifically targeting the various TGFβ receptors and downstream mediators. In this study we explore in primary chondrocytes the use of small molecule inhibitors to target TGFβ-induced pSmad1/5/9-, pSmad2/3- and TGFβ-activated kinase 1 (TAK1)-dependent signaling...
May 31, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28436712/disposition-and-metabolism-of-14-c-galunisertib-a-tgf-%C3%AE-ri-kinase-alk5-inhibitor-following-oral-administration-in-healthy-subjects-and-mechanistic-prediction-of-the-effect-of-itraconazole-on-galunisertib-pharmacokinetics
#19
Kenneth C Cassidy, Ivelina Gueorguieva, Colin Miles, Jessica Rehmel, Ping Yi, William J Ehlhardt
1. The disposition and metabolism of galunisertib (LY2157299 monohydrate, a TGF-βRI Kinase/ALK5 Inhibitor) was characterized following a single oral dose of 150 mg of [(14)C]-galunisertib (100 µCi) to six healthy human subjects. 2. The galunisertib plasma half-life was 8.6 h, while the (14)C half-life was 10.0 h. Galunisertib was abundant in circulation (40.3% of the (14)C AUC024 h), with 7 additional metabolites detected in plasma. Two metabolites LSN3199597 (M5, mono-oxidation), and M4 (glucuronide of M3) were the most abundant circulating metabolites (10...
May 16, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28405618/efficacy-of-alk5-inhibition-in-myelofibrosis
#20
Lanzhu Yue, Matthias Bartenstein, Wanke Zhao, Wanting Tina Ho, Ying Han, Cem Murdun, Adam W Mailloux, Ling Zhang, Xuefeng Wang, Anjali Budhathoki, Kith Pradhan, Franck Rapaport, Huaquan Wang, Zonghong Shao, Xiubao Ren, Ulrich Steidl, Ross L Levine, Zhizhuang Joe Zhao, Amit Verma, Pearlie K Epling-Burnette
Myelofibrosis (MF) is a bone marrow disorder characterized by clonal myeloproliferation, aberrant cytokine production, extramedullary hematopoiesis, and bone marrow fibrosis. Although somatic mutations in JAK2, MPL, and CALR have been identified in the pathogenesis of these diseases, inhibitors of the Jak2 pathway have not demonstrated efficacy in ameliorating MF in patients. TGF-β family members are profibrotic cytokines and we observed significant TGF-β1 isoform overexpression in a large cohort of primary MF patient samples...
April 6, 2017: JCI Insight
keyword
keyword
119505
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"