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https://www.readbyqxmd.com/read/29156422/syndecan-1-in-mechanosensing-of-nanotopological-cues-in-engineered-materials
#1
Victoria Le, Jason Lee, Somali Chaterji, Adrianne Spencer, Yen-Liang Liu, Peter Kim, Hsin-Chih Yeh, Deok-Ho Kim, Aaron B Baker
The cells of the vascular system are highly sensitive to biophysical cues from their local cellular microenvironment. To engineer improved materials for vascular devices and delivery of cell therapies, a key challenge is to understand the mechanisms that cells use to sense biophysical cues from their environment. Syndecans are heparan sulfate proteoglycans (HSPGs) that consist of a protein core modified with heparan sulfate glycosaminoglycan chains. Due to their presence on the cell surface and their interaction with cytoskeletal and focal adhesion associated molecules, cell surface proteoglycans are well poised to serve as mechanosensors of the cellular microenvironment...
November 9, 2017: Biomaterials
https://www.readbyqxmd.com/read/29142175/macrophage-differentiation-induced-by-pma-is-mediated-by-activation-of-rhoa-rock-signaling
#2
Lifeng Yang, Fan Dai, Lian Tang, Yulan Le, Wenjuan Yao
In order to investigate the effects of RhoA/ROCK signaling in macrophage differentiation, we used 100 ng/mL PMA to induce macrophage differentiation from U937 cells in vitro. The observation of cell morphology and the expression of CD68 and SR-A were performed to confirm the differentiation induced by PMA. Western blot analysis showed that the expression of ROCK1 and ROCK2 and the phosphorylation of MYPT1 were significantly increased after PMA treatment. Pulldown assay showed that the activation of RhoA was obviously enhanced when U937 cells were treated with PMA...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29130345/mir-199a-targeting-rock1-to-affect-kidney-cell-proliferation-invasion-and-apoptosis
#3
Zhigang Qin, Xin Wei, Ning Jin, Yao Wang, Rui Zhao, Yangqing Hu, Weijian Yan, Junke Li, Qiaoling Zhou
Renal cell carcinoma (RCC) is one of the three most common cancers of urinary tract cancer, accounting for 2-3% of all systemic cancers. Recent studies have found that miR-199a is lowly expressed in RCC, may act as a tumour suppressor gene to induce the occurrence of kidney cancer. In the present study, we investigated the role of miR-199a in the progression and metastasis of RCC. The results showed that miR-199a significantly downregulated in RCC and cell lines. Overexpression of miR-199a in RCC cell lines significantly inhibited cell proliferation, migration and invasion...
November 13, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29123196/identification-of-selection-signals-by-large-scale-whole-genome-resequencing-of-cashmere-goats
#4
Xiaokai Li, Rui Su, Wenting Wan, Wenguang Zhang, Huaizhi Jiang, Xian Qiao, Yixing Fan, Yanjun Zhang, Ruijun Wang, Zhihong Liu, Zhiying Wang, Bin Liu, Yuehui Ma, Hongping Zhang, Qianjun Zhao, Tao Zhong, Ran Di, Yu Jiang, Wei Chen, Wen Wang, Yang Dong, Jinquan Li
Inner Mongolia and Liaoning cashmere goats are two outstanding Chinese multipurpose breeds that adapt well to the semi-arid temperate grassland. These two breeds are characterized by their soft cashmere fibers, thus making them great models to identify genomic regions that are associated with cashmere fiber traits. Whole-genome sequencing of 70 cashmere goats produced more than 5.52 million single-nucleotide polymorphisms and 710,600 short insertions and deletions. Further analysis of these genetic variants showed some population-specific molecular markers for the two cashmere goat breeds that are otherwise phenotypically similar...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29115372/inhibition-of-rho-kinase-protects-against-colitis-in-mice-by-attenuating-intestinal-epithelial-barrier-dysfunction-via-mlc-and-the-nf-%C3%AE%C2%BAb-pathway
#5
Yanting Zou, Lili Ma, Yuan Zhao, Shuncai Zhang, Chaohui Zhou, Yu Cai
The aim of the present study was to investigate the role of Rho kinase (also known as ROCK) inhibitor in 2,4,6-trinitrobenzene sulfonic acid induced mouse colitis; and to elucidate the underlying mechanism of ROCK1/ROCK2 inhibition in enhancing intestinal epithelial barrier (IEB) function. A specific inhibitor of ROCK, Y-27632, was used to examine the role of ROCK in mouse colitis models. ROCK1 and ROCK2 were silenced respectively using RNA interference in Caco-2 cells. The expression of tight junction proteins and the downstream molecules of ROCK were assessed...
October 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29096333/distinct-ephb4-mediated-mechanisms-of-apoptotic-and-resistance-to-dasatinib-in-human-chronic-myeloid-leukemia-and-k562-cell-lines
#6
Wei-Hong Zhao, Bin-Tao Huang, Jian-Yu Zhang, Qing-Chun Zeng
OBJECTIVE: To determine the role and mechanism of EphB4 in dasatinib (DAS) resistance in advanced chronic myeloid leukemia (CML), we explored the EphB4-mediated apoptotic and matrix microenvironment pathway in human CML and K562 cell lines. METHOD: Heparinized bone marrow samples were obtained from enrolled five patients (identified as A to E and visits identified by number) at initial diagnosis (A1-E1) and in the DAS-resistance advanced phase (A2-E2). Meanwhile, highly DAS-resistant cells, named K562-R cells, were obtained from K562-W cells with increasing concentrations of DAS...
October 27, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29070696/structural-determinants-influencing-the-potency-and-selectivity-of-indazole-paroxetine-hybrid-g-protein-coupled-receptor-kinase-2-inhibitors
#7
Renee Bouley, Helen V Waldschmidt, M Claire Cato, Alessandro Cannavo, Jianliang Song, Joseph Y Cheung, Xin-Qiu Yao, Walter J Koch, Scott D Larsen, John J Tesmer
G protein-coupled receptor kinases (GRKs) phosphorylate activated receptors to promote arrestin binding, decoupling from heterotrimeric G proteins, and internalization. GRK2 and GRK5 are overexpressed in the failing heart and thus have become therapeutic targets. Previously, we discovered two classes of GRK2-selective inhibitors, one stemming from GSK180736A, a ROCK1 inhibitor, and the other from paroxetine, a selective serotonin-reuptake inhibitor. These two classes of compounds bind to the GRK2 active site in a similar configuration, but contain different hinge-binding "warheads": indazole and benzodioxole, respectively...
October 25, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/29039493/actein-induces-apoptosis-in-leukemia-cells-through-suppressing-rhoa-rock1-signaling-pathway
#8
Wen-Di Zhou, Xiang Wang, Xing-Zhen Sun, Jian Hu, Rong-Rong Zhang, Ze Hong
Actein is a tetracyclic triterpenoid compound, extracted from the rhizome of Cimicifuga foetida, exhibiting anticancer activities as previously reported. However, the effects of actein on human leukemia have not been explored before. In this study, the role of actein in regulating apoptosis induction in human leukemia cells was investigated. Actein administration significantly enhanced apoptosis, especially in human leukemia cell line of U937 and the primary human leukemia cells. The promotion was accompanied by caspase-9, caspase-3 and poly(ADP-ribose) polymerase (PARP) cleavage, and cytochrome c (Cyto-c) release...
October 10, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29029794/rho-kinase-inhibition-reverses-impaired-ca-2-handling-and-associated-left-ventricular-dysfunction-in-pressure-overload-induced-cardiac-hypertrophy
#9
Yusuf Olgar, Murat Cenk Celen, Bilge Eren Yamasan, Nihal Ozturk, Belma Turan, Semir Ozdemir
Recent studies have implicated a relationship between RhoA/ROCK activity and defective Ca(2+) homeostasis in hypertrophic hearts. This study investigated molecular mechanism underlying ROCK inhibition-mediated cardioprotection against pressure overload-induced cardiac hypertrophy, with a focus on Ca(2+) homeostasis. Cardiac hypertrophy model was established by performing transverse aortic constriction (TAC) in 8-week-old male rats. Groups were assigned as SHAM, TAC and TAC+Fas (rats undergoing TAC and treated with fasudil)...
November 2017: Cell Calcium
https://www.readbyqxmd.com/read/29027377/contribution-of-extracellular-matrix-and-signal-mechanotransduction-to-epithelial-cell-damage-in-inflammatory-bowel-disease-patients-a-proteomic-study
#10
Manuela Moriggi, Luca Pastorelli, Enrica Torretta, Gian Eugenio Tontini, Daniele Capitanio, Stefano Ferrero Bogetto, Maurizio Vecchi, Cecilia Gelfi
This study utilized 2D-DIGE, isotope-coded protein labelling (ICPL) and biochemical assays to characterize protein alteration in Ulcerative Colitis (UC) and Crohn's Disease (CD) in human epithelial cell and mucosal biopsies in Inflammatory Bowel Disease (IBD)-affected patients. The aim of this study is to identify the key molecular signatures involved in epithelial cell structure of IBDs. In non-inflamed UC (QUC) keratins, vimentin and FAK increased, whereas vinculin and de-tyrosinated α-tubulin decreased; inflammation (IUC) exacerbated molecular changes, being COL6A1, tenascin-C and vimentin increased...
October 13, 2017: Proteomics
https://www.readbyqxmd.com/read/29024000/myeloid-notch1-deficiency-activates-rhoa-rock-pathway-and-aggravates-hepatocellular-damage-in-mouse-ischemic-livers
#11
Ling Lu, Shi Yue, Longfeng Jiang, Changyong Li, Qiang Zhu, Michael Ke, Hao Lu, Xuehao Wang, Ronald W Busuttil, Qi-Long Ying, Jerzy W Kupiec-Weglinski, Bibo Ke
Notch signaling plays an emerging role in the regulation of immune cell development and function during inflammatory response. Activation of the ras homolog gene family, member A (RhoA)/Rho-associated protein kinase (ROCK) pathway promotes leukocyte accumulation in tissue injury. However, it remains unknown whether Notch signaling regulates RhoA/ROCK-mediated immune responses in liver ischemia and reperfusion injury (IRI). This study investigated intracellular signaling pathways regulated by Notch receptors in the IR-stressed liver and in vitro...
October 12, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28978024/mir-199a-b-5p-inhibits-hepatocellular-carcinoma-progression-by-post-transcriptionally-suppressing-rock1
#12
Yangyang Zhan, NanXin Zheng, Fei Teng, Leilei Bao, Fang Liu, Mingjian Zhang, Meng Guo, Wenyuan Guo, Guoshan Ding, Quanxing Wang
In this study, we explored the actions of miR-199a/b-5p during hepatocellular carcinoma (HCC) progression and its potential target genes. Through heatmap miRNA expression analysis of 15 matched HCC tumor and adjacent non-tumor liver tissues from the TCGA database, we detected 19 mRNAs that were upregulated and 13 that were downregulated specifically in HCC. Among these, miR-199 family members were downregulated in HCC tumors and cell lines, as compared to controls. Low miR-199a/b-5p expression was also associated with poor overall survival of HCC patients...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28972449/targeting-rock-activity-to-disrupt-and-prime-pancreatic-cancer-for-chemotherapy
#13
Claire Vennin, Nicola Rath, Marina Pajic, Michael F Olson, Paul Timpson
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease; the identification of novel targets and development of effective treatment strategies are urgently needed to improve patient outcomes. Remodeling of the pancreatic stroma occurs during PDAC development, which drives disease progression and impairs responses to therapy. The actomyosin regulatory ROCK1 and ROCK2 kinases govern cell motility and contractility, and have been suggested to be potential targets for cancer therapy, particularly to reduce the metastatic spread of tumor cells...
October 3, 2017: Small GTPases
https://www.readbyqxmd.com/read/28945203/mtorc1-loss-impairs-epidermal-adhesion-via-tgf-%C3%AE-rho-kinase-activation
#14
Kaushal Asrani, Akshay Sood, Alba Torres, Dan Georgess, Pornima Phatak, Harsimar Kaur, Amber Dubin, C Conover Talbot, Loubna Elhelu, Andrew J Ewald, Bo Xiao, Paul Worley, Tamara L Lotan
Despite its central position in oncogenic intracellular signaling networks, the role of mTORC1 in epithelial development has not been studied extensively in vivo. Here, we have used the epidermis as a model system to elucidate the cellular effects and signaling feedback sequelae of mTORC1 loss of function in epithelial tissue. In mice with conditional epidermal loss of the mTORC1 components Rheb or Rptor, mTORC1 loss of function unexpectedly resulted in a profound skin barrier defect with epidermal abrasions, blistering, and early postnatal lethality, due to a thinned epidermis with decreased desmosomal protein expression and incomplete biochemical differentiation...
September 25, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28938647/long-non-coding-rna-malat1-for-promoting-metastasis-and-proliferation-by-acting-as-a-cerna-of-mir-144-3p-in-osteosarcoma-cells
#15
Yong Wang, Yueyang Zhang, Tao Yang, Wei Zhao, Ningning Wang, Pengcheng Li, Xiandong Zeng, Weiguo Zhang
Long non-coding RNAs (lncRNAs) are involved in various biological processes and diseases including osteosarcoma. Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is overly expressed in osteosarcoma. But the function and mechanism it works on in osteosarcoma proliferation and metastasis mediated by Rho associated coiled-coil containing protein kinase 1 (ROCK1) and Rho associated coiled-coil containing protein kinase 2 (ROCK2) remain unclear. In the present study, an elevated MALAT1 was found in osteosarcoma tissues and cell lines, and the elevated MALAT1 was correlated with a poor prognosis in osteosarcoma patients...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28928287/hif-3%C3%AE-promotes-metastatic-phenotypes-in-pancreatic-cancer-by-transcriptional-regulation-of-the-rhoc-rock1-signaling-pathway
#16
Xianfei Zhou, Xingjun Guo, Meiyuan Chen, Chencheng Xie, Jianxin Jiang
Hypoxia contributes to pancreatic cancer progression and promotes its growth and invasion. Previous research principally focused on hypoxia-inducible factor-1 alpha and HIF-2α (HIF1A and EPAS1) as the major hypoxia-associated transcription factors in pancreatic cancer. However, the role of HIF-3α (HIF3A) has not been investigated. Therefore, HIF-1α, HIF-2α, and HIF-3α expression levels were measured under normoxic and hypoxic conditions. In addition, HIF-3α expression was measured in human pancreatic cancer tissue specimens and the impact of altered HIF-3α expression on cell invasion and migration was investigated in vitro and in vivo, as well as the underlying mechanisms...
September 19, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28926926/protective-effects-of-aloperin-on-monocroline-induced-pulmonary-hypertension-via-regulation-of-rho-a-rho-kinsase-pathway-in-rats
#17
Fan Wu, Wanxia Yao, Jiamei Yang, Min Zhang, Yanping Xu, Yinju Hao, Lin Yan, Yang Niu, Tao Sun, Jianqiang Yu, Ru Zhou
Pulmonary hypertension (PH) is fatal disease which closely involves Rho A/ Rho kinsase (ROCK) pathway. Aloperine is a main active alkaloid extracted from Sophora alopecuroides, which is a traditional Chinese herbal medicine that has been used widely. However, the effects of this alkaloid on pulmonary hypertension and its mechanisms remain unclear. Therefore, this study is designed to investigate whether aloperine has protective effects on PH induced by monocrotaline, whether these effects may be related to regulation of RhoA/ROCK pathway in rats...
November 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28923399/up-regulation-of-rho-associated-kinase-1-2-by-glucocorticoids-promotes-migration-invasion-and-metastasis-of-melanoma
#18
Gao-Xiang Huang, Yan Wang, Jie Su, Peng Zhou, Bo Li, Li-Juan Yin, Jian Lu
Although glucocorticoids (GCs) regulate proliferation, differentiation and apoptosis of tumor cells, their influence on metastasis of tumor cells is poorly understood. Melanoma is a type of skin cancers with high metastasis. We investigated the effect of GCs on metastasis of melanoma cells and its mechanism. We found that GCs significantly promoted the adhesion, migration, invasion of melanoma cells in vitro and lung metastasis in experimental melanoma metastasis mice. Dexamethasone (Dex), a synthetic GC, did not change the RhoA, RhoB and RhoC signalings, but significantly increased the expression and activity of Rho-associated kinase 1/2 (ROCK1/2)...
September 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28901478/microrna%C3%A2-195-inhibits-cell-proliferation-migration-and-invasion-in-laryngeal-squamous-cell-carcinoma-by-targeting-rock1
#19
Yang Liu, Jixiang Liu, Lin Wang, Xiangli Yang, Xiang Liu
Laryngeal carcinoma is the second most common malignancy of the head and neck cancers. The most common type of laryngeal carcinoma comprises laryngeal squamous cell carcinoma (LSCC), which accounts for ~95% of laryngeal carcinoma cases. Despite great progress in diagnostic and therapeutic techniques over the last few decades, the prognosis for patients with LSCC remains poor. A number of studies reported that various miRNAs are dysregulated in LSCC and serve critical roles in LSCC tumorigenesis and tumor development...
November 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28899000/rhoa-rock-signalling-is-necessary-for-lateralization-and-differentiation-of-the-developing-sinoatrial-node
#20
Rebecca Vicente-Steijn, Tim P Kelder, Leon G Tertoolen, Lambertus J Wisse, Daniël A Pijnappels, Robert E Poelmann, Martin J Schalij, Marco C deRuiter, Adriana C Gittenberger-de Groot, Monique R M Jongbloed
Aims: RHOA-ROCK signalling regulates cell migration, proliferation, differentiation, and transcription. RHOA is expressed in the developing cardiac conduction system in chicken and mice. In early development, the entire sinus venosus myocardium, including both the transient left-sided and the definitive sinoatrial node (SAN), has pacemaker potential. Later, pacemaker potential is restricted to the right-sided SAN. Disruption of RHOA expression in adult mice causes arrhythmias including bradycardia and atrial fibrillation, the mechanism of which is unknown but presumed to affect the SAN...
August 1, 2017: Cardiovascular Research
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