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Nancy M Lee, Cevat Erisken, Thomas Iskratsch, Michael Sheetz, William N Levine, Helen H Lu
Physiologically relevant models of wound healing are essential for understanding the biology of connective tissue repair and healing. They can also be used to identify key cellular processes and matrix characteristics critical for the design of soft tissue grafts. Modeling the various stages of repair post tendon injury, polymer meshes of varying fiber diameter (nano-1 (390 nm) < nano-2 (740 nm) < micro (1420 nm)) were produced. Alignment was also introduced in the nano-2 group to model matrix undergoing biological healing rather than scar formation...
October 12, 2016: Biomaterials
Hongyu Sun, Jiajia Tang, Yongchao Mou, Jing Zhou, Linlin Qu, Kayla Duval, Zhu Huang, Ning Lin, Ruiwu Dai, Chengxiao Liang, Zi Chen, Lijun Tang, Fuzhou Tian
: Carbon nanotube (CNT)-based hydrogels have been shown to support cardiomyocyte growth and function. However, their role in cellular integrity among cardiomyocytes has not been studied in detail and the mechanisms underlying this process remain unclear. Here, single walled CNTs incorporated into gelatin with methacrylate anhydride (CNT/GelMA) hydrogels were utilized to construct cardiac tissues, which enhanced cardiomyocyte adhesion and maturation. Furthermore, through the use of immunohistochemical staining, transmission electron microscopy and intracellular calcium transient measurement, the incorporation of CNTs into the scaffolds was observed to markedly enhance the assembly and formation in the cardiac constructs...
October 18, 2016: Acta Biomaterialia
Jolanda van Hengel, Celine Van den Broeke, Tim Pieters, Louis Libbrecht, Ilse Hofmann, Frans van Roy
p120 catenin (p120ctn) is required for the stability of classic cadherins at the cell surface and is thought to play a central role in modulating cell-cell adhesion. Cytoplasmic p120ctn promotes cell motility, and probably other activities, by modulating the activities of RhoA, Rac and Cdc42. E-cadherin is expressed in periportal but not in perivenous hepatocytes. In contrast, all hepatocytes of normal mouse liver express N-cadherin. Cholangiocytes express exclusively E-cadherin. Mice with p120ctn ablation in hepatocytes and cholangiocytes (p120LiKO mice) were generated by Cre-loxP technology...
October 15, 2016: European Journal of Cell Biology
Ana Rolo, Sarah Escuin, Nicholas D E Greene, Andrew J Copp
Neural tube closure is an important morphogenetic event that involves dramatic reshaping of both neural and non-neural tissues. Rho GTPases are key cytoskeletal regulators involved in cell motility and in several developmental processes, and are thus expected to play pivotal roles in neurulation. Here, we discuss 2 recent studies that shed light on the roles of distinct Rho GTPases in different tissues during neurulation. RhoA plays an essential role in regulating actomyosin dynamics in the neural epithelium of the elevating neural folds, while Rac1 is required for the formation of cell protrusions in the non-neural surface ectoderm during neural fold fusion...
October 21, 2016: Small GTPases
Hui-Ju Tsai, Ching-Ping Tseng
Multiple functions of platelets in various physiological and pathological conditions have prompted considerable attention on understanding how platelets are generated and activated. Of the adaptor proteins that are expressed in megakaryocytes and platelets, Disabled-2 (Dab2) has been demonstrated in the past decades as a key regulator of platelet signaling. Dab2 has two alternative splicing isoforms p82 and p59. However, the mode of Dab2's action remains to be clearly defined. In this review, we highlight the current understanding of Dab2 expression and function in megakaryocytic differentiation, platelet activation and integrin signaling...
2016: Thrombosis Journal
Pieter Uvin, Maarten Albersen, Ine Bollen, Maarten Falter, Emmanuel Weyne, Loes Linsen, Hanna Tinel, Peter Sandner, Trinity J Bivalacqua, Dirk Jmk De Ridder, Frank Van der Aa, Bert Brône, Koenraad Van Renterghem
OBJECTIVES: To evaluate the expression of the Rho/Rho associated protein kinase (ROCK) pathway in corpus cavernosum of patients with severe erectile dysfunction (ED) compared to healthy human corpus cavernosum, and to test the functional effects of two Rho Kinase Inhibitors (RKI) on erectile tissue of patients with severe ED, not responding to phosphodiesterase type 5 inhibitors (PDE5-i). PATIENTS AND METHODS: Human corpus cavernosum samples were obtained after consent from individuals undergoing penile prosthesis implantation (n = 7 for organ bath experiments, n = 17 for qPCR)...
October 20, 2016: BJU International
Joseph T Tarr, Timothy G Visser, Joanne E Moon, Honey Hendesi, Mary F Barbe, James P Bradley, Steven N Popoff
Mammalian palatogenesis is a complex process involving a temporally and spatially regulated myriad of factors. Together these factors control the 3 vital processes of proliferation, elevation and fusion of the developing palate. In this study, we show for the first time the unequivocally vital role of CCN2 in development of the mammalian palate. We utilized CCN2 knockout (KO) mice and cranial neural crest derived mesenchymal cells from these CCN2 KO mice to investigate the 3 processes crucial to normal palatogenesis...
October 20, 2016: Journal of Cell Communication and Signaling
Hyun Jun Jung, Tae-Hwan Kwon
Kidney collecting duct is an important renal tubular segment for regulation of body water homeostasis and urine concentration. Water reabsorption in the collecting duct principal cells is controlled by vasopressin, a peptide hormone which induces the osmotic water transport across the collecting duct epithelia through regulation of water channel proteins aquaporin-2 (AQP2) and aquaporin-3 (AQP3). In particular, vasopressin induces both intracellular translocation of AQP2-bearing vesicles to the apical plasma membrane and transcription of Aqp2 gene to increase AQP2 protein abundance...
October 19, 2016: American Journal of Physiology. Renal Physiology
Jessica M Wilson, Jeremy W Prokop, Ellen Lorimer, Elizabeth Ntantie, Carol L Williams
Two isoforms of the small GTPase Rap1, Rap1A and Rap1B, participate in cell adhesion; Rap1A promotes steady state adhesion, while Rap1B regulates dynamic changes in cell adhesion. These events depend on the prenylation of Rap1, which promotes its membrane localization. Here, we identify previously unsuspected differences in the regulation of prenylation of Rap1A versus Rap1B, due in part to their different phosphorylation-dependent interactions with the chaperone protein SmgGDS-607. Previous studies indicate that activation of Gαs protein-coupled receptors (GPCRs) phosphorylates S-179 and S-180 in the polybasic region (PBR) of Rap1B, which inhibits Rap1B binding to SmgGDS-607 and diminishes Rap1B prenylation and membrane localization...
October 16, 2016: Journal of Molecular Biology
Takayoshi Kaida, Hidetoshi Nitta, Yuki Kitano, Kensuke Yamamura, Kota Arima, Daisuke Izumi, Takaaki Higashi, Junji Kurashige, Katsunori Imai, Hiromitsu Hayashi, Masaaki Iwatsuki, Takatsugu Ishimoto, Daisuke Hashimoto, Yoichi Yamashita, Akira Chikamoto, Takahisa Imanura, Takatoshi Ishiko, Toru Beppu, Hideo Baba
PURPOSE: Anaphylatoxin C5a is a strong chemoattractant of the complement system that binds the C5a receptor (C5aR). The expression of C5aR is associated with poor prognosis in several cancers. However, the role of C5aR in gastric cancer (GC) is unknown. The aim of this study was to examine the role of C5aR on GC cell motility and invasion. EXPERIMENTAL DESIGN: The mechanism of invasion via C5aR was assessed by analyzing cytoskeletal rearrangement and RhoA activity after C5a treatment...
October 14, 2016: Oncotarget
A Mardomi, M Sabzichi, M Hussein Somi, D Shanehbandi, R Rahbarghazi, O Taj Sanjarani, N Samadi
Mesenchymal stem cells (MSCs) display differential migration ability toward different tumor-released factors. Migration of MSCs is highly important in induction of proliferation and invasiveness of hepatocellular carcinoma (HepG2) cells. In this study, the role of CXCR4/CXCL12 axis and TGF-βR signaling were evaluated in the migration of MSCs toward HepG2 cells. The MSCs were incubated with SDF-1α (CXCL12), antagonists of CXCR4, TGF-βR, and co-receptor of TGF-β, (endoglin) for 48h. Then, the migration of these cells toward HepG2 cells was analyzed using in vitro migration assay...
September 30, 2016: Cellular and Molecular Biology
Alberto García-Mariscal, Karine Peyrollier, Astrid Basse, Esben Pedersen, Ralph Rühl, Jolanda van Hengel, Cord Brakebusch
The ubiquitously expressed small GTPase RhoA is essential for embryonic development and mutated in different cancers. Functionally, it is well described as a regulator of the actin cytoskeleton, but its role in gene regulation is less understood. Using primary mouse keratinocytes with a deletion of the RhoA gene, we have now been exploring how the loss of RhoA affects gene expression. Performing transcription factor reporter assays, we found a significantly decreased activity of a RAR luciferase reporter in RhoA-null keratinocytes...
October 18, 2016: Small GTPases
Haruka Handa, Ari Hashimoto, Shigeru Hashimoto, Hisataka Sabe
Modes of cancer invasion interchange between the mesenchymal type and amoeboid type in response to the microenvironment, in which RhoA and Rac1 are selectively required to perform different modes of actin-cytoskeletal remodeling. Membrane remodeling is another integral part of invasion. Arf6 regulates the recycling of molecules at the cell periphery, and is often overexpressed in malignant cancers together with its effector AMAP1/ASAP1/DDEF1. This pathway promotes mesenchymal-type invasion when AMAP1 binds to EPB41L5, a mesenchymal-specific protein induced by ZEB1...
October 18, 2016: Small GTPases
Caojian Zuo
OBJECTIVE: Cardiac fibroblasts play a vital role in the progression of fibrotic cardiac remodeling in hypertensive and failing heart. Osteoglycin (OGN) is implicated as a key regulator of left ventricular mass. However, its precise molecular role in cardiac fibrosis remains unknown. This study aims to investigate the impact of OGN in hypertensive cardiac remodeling. DESIGN AND METHOD: OGN deficient mice and its wildtype (WT) littermates were subjected to either angiotensin II (Ang II) infusion or pressure overload induced by transverse aortic constriction (TAC)...
September 2016: Journal of Hypertension
Shi-Fa Zhang, Yan Zhou, Kai-Jing Zhang, Jia-Jie Luan, Shi-Mei Qi
OBJECTIVE: To investigate the effect of Nogo-66 receptor (NgR) silencing with specific small interfering RNA (siRNA) on brain injury repair in preterm rats with brain injury caused by intrauterine infection and related mechanism of action. METHODS: The pregnant Sprague-Dawley rats (with a gestational age of 15 days) were selected, and premature delivery was induced by RU486 or lipopolysaccharide (LPS). The preterm rats delivered by those treated with RU486 were selected as the control group...
October 2016: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
Anne Blangy
Tensins are focal adhesion molecules that were identified and characterized in the late 1980's - early 1990's. They play an essential role in the control of cell adhesion. Tensins can bind the tail of ß integrin via their Phospho Tyrosine Binding (PTB) domain, they exhibit various protein interaction domains including a Src Homology 2 (SH2) domain and they are serine-, threonine- and tyrosine-phosphorylated in response to various stimuli. Tensins serve as scaffolds to gather signaling molecules at the extracellular matrix adhesion complexes...
October 17, 2016: Biology of the Cell
Kangwook Lee, Sung-Gook Cho, Sang-Mi Woo, Ah Jeong Kim, Kang Min Lee, Ho Yeon Go, Seung-Ho Sun, Tae-Hun Kim, Ki-Yong Jung, You-Kyung Choi, Eun Mee Lim, Yun-Kyung Song, Jong-Hyeong Park, Chan-Yong Jun, Seong-Gyu Ko
Danggui-Sayuk-Ga-Osuyu-Senggang-Tang (DSGOST), one of the traditional Chinese medicines, has long been prescribed for patients suffering from Raynaud phenomenon (RP) in Northeast Asian countries, including China, Japan and Korea. Although a previous in vitro study from our laboratory revealed that DSGOST prevents cold (25˚C)‑induced RhoA activation and endothelin‑1 (ET‑1) production in endothelial cells (ECs), the mechanisms by which DSGOST is able to alleviate the symptoms of RP have yet to be fully elucidated...
October 5, 2016: Molecular Medicine Reports
Nadia Soudani, Crystal M Ghantous, Zein Farhat, Wassim N Shebaby, Kazem Zibara, Asad Zeidan
Background and Aims: Hypertension and obesity are important risk factors of cardiovascular disease. They are both associated with high leptin levels and have been shown to promote vascular hypertrophy, through the RhoA/ROCK and ERK1/2 phosphorylation. Calcineurin/NFAT activation also induces vascular hypertrophy by upregulating various genes. This study aimed to decipher whether a crosstalk exists between the RhoA/ROCK pathway, Ca(2+)/calcineurin/NFAT pathway, and ERK1/2 phosphorylation in the process of mechanical stretch-induced vascular smooth muscle cell (VSMC) hypertrophy and leptin synthesis...
2016: Frontiers in Physiology
Claire-Anne Gutekunst, Jack K Tung, Margaret E McDougal, Robert E Gross
Regrowth inhibitory molecules prevent axon regeneration in the adult mammalian central nervous system (CNS). RhoA, a small GTPase in the Rho family, is a key intracellular switch that mediates the effects of these extracellular regrowth inhibitors. The bacterial enzyme C3-ADP ribosyltransferase (C3) selectively and irreversibly inhibits the activation of RhoA and stimulates axon outgrowth and regeneration. However, effective intracellular delivery of the C3 protein in vivo is limited by poor cell permeability and a short duration of action...
October 13, 2016: Neuroscience
Benoît Peyronnet, Thomas Seisen, Véronique Phé, Vincent Misrai, Alexandre de la Taille, Morgan Rouprêt
AIM: To provide a systematic review of epidemiological data regarding the association between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) in men. SEARCH STRATEGY: A research has been conducted on the Medline database using the keywords: ("erectile dysfunction" or "sexual dysfunction") and ("benign prostatic hyperplasia" or "lower urinary tract symptoms"). The eligibility of studies was defined using the PICOS method in accordance with the PRISMA statement...
October 10, 2016: La Presse Médicale
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