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A J Korzekwa, M Łupicka, B M Socha, A A Szczepańska
Adenomyosis is defined as the presence of glandular foci external to the endometrium of the uterus, either in the myometrium or/and perimetrium, depending on the progress of this dysfunction. To date, we showed that steroids secretion and prolactin expression and proliferative processes are disturbed during uterine adenomyosis in cows. During endometriosis in eutopic endometrium in women, gap junctions are down regulated. The transmembrane gap junction protein, connexin (Cx43) is necessary for endometrial morphological, biochemical and angiogenic functions...
September 1, 2016: Polish Journal of Veterinary Sciences
Zhao-Wei Zou, Hai-Jin Chen, Jin-Long Yu, Zong-Hai Huang, Shun Fang, Xiao-Hua Lin
Chemotherapy is one of the most commonly used therapeutic strategies for metastatic colon cancer. However, the development of resistance to chemotherapeutic agents limits their application in clinical use. The underlying mechanisms of this resistance development require further elucidation. The current study investigated the effects of connexin43 (Cx43) gap junctions on 5‑fluorouracil (5‑FU), oxaliplatin and irinotecan in colon cancer cells. Three different methods were used to manipulate Cx43 gap junction function: i) Cell culture at different densities; ii) pretreatment with a Cx43 specific inhibitor or enhancer; and iii) Cx43 gene knock‑down...
October 6, 2016: Molecular Medicine Reports
Tania Martins-Marques, Maria Joao Pinho, Monica Zuzarte, Carla Oliveira, Paulo Pereira, Joost P G Sluijter, Celia Gomes, Henrique Girao
Extracellular vesicles (EVs) are major conveyors of biological information, mediating local and systemic cell-to-cell communication under physiological and pathological conditions. These endogenous vesicles have been recognized as prominent drug delivery vehicles of several therapeutic cargoes, including doxorubicin (dox), presenting major advantages over the classical approaches. Although dox is one of the most effective anti-tumour agents in the clinical practice, its use is very often hindered by its consequent dramatic cardiotoxicity...
2016: Journal of Extracellular Vesicles
Raquel Gago-Fuentes, John F Bechberger, Marta Varela-Eirin, Adrian Varela-Vazquez, Benigno Acea, Eduardo Fonseca, Christian C Naus, Maria D Mayan
Chondrocytes in cartilage and bone cells population express connexin43 (Cx43) and gap junction intercellular communication (GJIC) is essential to synchronize cells for coordinated electrical, mechanical, metabolic and chemical communication in both tissues. Reduced Cx43 connectivity decreases chondrocyte differentiation and defective Cx43 causes skeletal defects. The carboxy terminal domain (CTD) of Cx43 is located in the cytoplasmic side and is key for protein functions. Here we demonstrated that chondrocytes from the CTD-deficient mice, K258stop/Cx43KO and K258stop/K258stop, have reduced GJIC, increased rates of proliferation and reduced expression of collagen type II and proteoglycans...
September 22, 2016: Oncotarget
Tze-Wen Chung, Hsin-Yu Lo, Tzung-Han Chou, Jan-Hou Chen, Shoei-Shen Wang
Bone marrow-derived mesenchymal stem cell microtissues (BMSCMT) enhanced cardiomyogenesis in vitro and cardiac repairs of myocardial infarcted hearts in vivo are documented. Producing human BMSCMT onto patches in vitro for cardiac tissue engineering has not been reported. For possibly producing human bone marrow-derived mesenchymal stem cell microtissues (hBMSCMT) on an elastic silk fibroin (SF)-poly(ε-caprolactone) (PCL) based patches is hereby designed. After an elastic SF-PCL (SP) patch is fabricated, hyaluronic acid (HA)/SF-PCL(HSP) and HA-GRGD/SF-PCL(HGSP) patches are fabricated by photochemically grafting HA and HA-GRGD onto SP surfaces...
September 28, 2016: Macromolecular Bioscience
Sied Kebir, Zacharias Orfanos, Julia Schuld, Markus Linhart, Christian Lamberz, Peter F M van der Ven, Jan Schrickel, Gregor Kirfel, Dieter O Fürst, Rainer Meyer
Pressure overload induces cardiac remodeling involving both the contractile machinery and intercalated disks (IDs). Filamin C (FlnC) and Xin actin-binding repeat-containing proteins (XIRPs) are multi-adapters localizing in IDs of higher vertebrates. Knockout of the gene encoding Xin (Xirp1) in mice leads to a mild cardiac phenotype with ID mislocalization. In order to amplify this phenotype, we performed transverse aortic constriction (TAC) on control and Xirp1-deficient mice. TAC induced similar left ventricular hypertrophy in both genotypes, suggesting that the lack of Xin does not lead to higher susceptibility to cardiac overload...
October 15, 2016: Experimental Cell Research
Yilin Mao, Ryan S Tonkin, Tara Nguyen, Simon J O'Carroll, Louise F B Nicholson, Colin R Green, Gila Moalem-Taylor, Catherine A Gorrie
Blocking of Connexin43 hemichannels, the main gap junction protein located on astrocytes in the central nervous system, has been shown to reduce neural injury in a number of models. We demonstrated previously that local administration of a Connexin43 mimetic peptide, Peptide5, reduces secondary tissue damage after spinal cord injury (SCI). Here, we investigated whether acute systemic delivery of Peptide5 is also protective in a model of SCI. Rats were subjected to a mild spinal cord contusion using the Multicentre Animal Spinal Cord Injury Study impactor and were injected intraperitoneally with Peptide5 or a scrambled peptide immediately and at 2 h and 4 h post-injury...
October 13, 2016: Journal of Neurotrauma
Tone A Fykerud, Lars M Knudsen, Max Z Totland, Vigdis Sørensen, Shiva Dahal-Koirala, Ragnhild A Lothe, Andreas Brech, Edward Leithe
In order to achieve accurate chromosome segregation, eukaryotic cells undergo a dramatic change in morphology to obtain a spherical shape during mitosis. Interphase cells communicate directly with each other by exchanging ions and small molecules via gap junctions, which have important roles in controlling cell growth and differentiation. As cells round up during mitosis, the gap junctional communication between mitotic cells and adjacent interphase cells ceases. Whether mitotic cells use alternative mechanisms for mediating direct cell-cell communication during rounding is currently unknown...
September 13, 2016: Cell Cycle
Kristin M French, Joshua T Maxwell, Srishti Bhutani, Shohini Ghosh-Choudhary, Marcos J Fierro, Todd D Johnson, Karen L Christman, W Robert Taylor, Michael E Davis
Cardiac progenitor cells (CPCs) have rapidly advanced to clinical trials, yet little is known regarding their interaction with the microenvironment. Signaling cues present in the microenvironment change with development and disease. This work aims to assess the influence of two distinct signaling moieties on CPCs: cyclic biaxial strain and extracellular matrix. We evaluate four endpoints for improving CPC therapy: paracrine signaling, proliferation, connexin43 expression, and alignment. Vascular endothelial growth factor A (about 900 pg/mL) was secreted by CPCs cultured on fibronectin and collagen I...
2016: Stem Cells International
David Sedmera, Jan Neckar, Jiri Benes, Jana Pospisilova, Jiri Petrak, Kamil Sedlacek, Vojtech Melenovsky
Volume overload leads to development of eccentric cardiac hypertrophy and heart failure. In our previous report, we have shown myocyte hypertrophy with no fibrosis and decrease in gap junctional coupling via connexin43 in a rat model of aorto-caval fistula at 21 weeks. Here we set to analyze the electrophysiological and protein expression changes in the left ventricle and correlate them with phenotypic severity based upon ventricles to body weight ratio. ECG analysis showed increased amplitude and duration of the P wave, prolongation of PR and QRS interval, ST segment elevation and decreased T wave amplitude in the fistula group...
2016: Frontiers in Physiology
Bryan C Ampey, Timothy J Morschauser, Jayanth Ramadoss, Ronald R Magness
Uterine vascular adaptations facilitate rises in uterine blood flow during pregnancy, which are associated with gap junction connexin (Cx) proteins and endothelial nitric oxide synthase. In uterine artery endothelial cells (UAECs), ATP activates endothelial nitric oxide synthase in a pregnancy (P)-specific manner that is dependent on Cx43 function. Caveolar subcellular domain partitioning plays key roles in ATP-induced endothelial nitric oxide synthase activation and nitric oxide production. Little is known regarding the partitioning of Cx proteins to caveolar domains or their dynamics with ATP treatment...
October 2016: Hypertension
Yuan Chi, Xiling Zhang, Zhen Zhang, Takahiko Mitsui, Manabu Kamiyama, Masayuki Takeda, Jian Yao
Connexin (Cx) hemichannels regulate many cellular processes with little information available regarding their mechanisms. Given that many pathological factors that activate hemichannels also disrupts the integrity of cellular junctions, we speculated a potential participation of hemichannels in the regulation of cell junctions. Here we tested this hypothesis. Exposure of renal tubular epithelial cells to Ca(2+)-free medium led to disassembly of tight and adherens junctions, as indicated by the reduced level of ZO-1 and cadherin, disorganization of F-actin, and severe drop in transepithelial electric resistance...
August 21, 2016: Redox Biology
Udi Sarig, Hadar Sarig, Elio de-Berardinis, Su-Yin Chaw, Evelyne B V Nguyen, Vaibavi S Ramanujam, Vu D Thang, Muthafar Al-Haddawi, Susan Liao, Dror Seliktar, Theodoros Kofidis, Freddy Y C Boey, Subbu S Venkatraman, Marcelle Machluf
OBJECTIVE: To evaluate the regenerative capacity of non-supplemented and bioactive patches made of decellularized porcine cardiac extracellular matrix (pcECM) and characterize the biological key factors involved in possible cardiac function (CF) restoration following acute and 8weeks chronic MI. BACKGROUND: pcECM is a key natural biomaterial that can affect cardiac regeneration following myocardial infarction (MI), through mechanisms, which are still not clearly understood...
October 15, 2016: Acta Biomaterialia
Martina Maass, Benjamin Krausgrill, Simon Eschrig, Tobias Kaluschke, Katja Urban, Gabriel Peinkofer, Tobias G Plenge, Simon Oeckenpöhler, Martin Raths, Dennis Ladage, Marcel Halbach, Jürgen Hescheler, Jochen Müller-Ehmsen
Cardiac cell replacement therapy is a promising therapy to improve cardiac function in heart failure. Persistence, structural and functional maturation and integration of transplanted cardiomyocytes into recipient's hearts are crucial for a safe and efficient replacement of lost cells. We studied histology, electrophysiology and quantity of intramyocardially transplanted rat neonatal cardiomyocytes (NCM) and performed a detailed functional study with repeated invasive (pressure-volume-catheter) and non-invasive (echocardiography) analyses of infarcted female rat hearts including pharmacological stress before and 3 weeks after intramyocardial injection of 5x10(6) (low-NCM) or 25x10(6) (high-NCM) syngeneic male NCM or medium as placebo (Ctrl)...
August 17, 2016: Cell Transplantation
Youbin Chen, Jiankun Xu, Haojie Liao, Zebin Ma, Yuantao Zhang, Hongjiang Chen, Zhonglian Huang, Jun Hu
As a type of mechanical stimulation, extracorporeal shockwave (ESW) has been widely used in the clinic to treat bone fracture delayed union and non-unions. A large number of studies have shown beneficial effects of ESW in promoting fracture healing by inducing bone regeneration; however, the underlying mechanisms remain unclear. ESW has been shown to induce the production of prostaglandin E2 (PGE2), which is essential for gap junction intercellular communication in response to mechanical stress. Among the 19 known gap junction subunits, connexin43 (Cx43) is the most prevalent for mediating the response of mechanical stress...
September 2016: Medical Hypotheses
Younho Han, Dong Hyeok Cho, Dong Jin Chung, Kwang Youl Lee
Osterix is an essential transcription factor for osteogenesis and is expressed in osteoblasts. Although Osterix has been shown to be induced by bone morphogenetic protein 4, the molecular mechanism underlying Osterix function during osteoblast differentiation remains unclear. Connexin43 (Cx43) is the most abundant gap junction protein in bone cells and plays a critical role in osteoblast differentiation. However, little is known about the functional interactions between Osterix and the Cx43 promoter. In the present study, we investigated the relationship between Osterix and Cx43 in HEK293 and C2C12 cells...
September 16, 2016: Biochemical and Biophysical Research Communications
Cindy X Guo, Mohd N Mat Nor, Helen V Danesh-Meyer, Kirstan A Vessey, Erica L Fletcher, Simon J O'Carroll, Monica L Acosta, Colin R Green
PURPOSE: Drugs that regulate connexin43 (Cx43) gap junction channels can reduce the spread of injury and improve functional outcomes after nervous system trauma. In the eye, Cx43 expression increases in the choroid following light damage. The aim of this study was to investigate whether Cx43 hemichannel block could preserve retinal function postinjury. METHODS: Light damage was induced by exposure of adult albino Sprague-Dawley rats to 2700 Lux light for 24 hours...
August 1, 2016: Investigative Ophthalmology & Visual Science
Heiko Lemcke, Janine Peukert, Natalia Voronina, Anna Skorska, Gustav Steinhoff, Robert David
Small antisense RNAs like miRNA and siRNA are of crucial importance in cardiac physiology, pathology and, moreover, can be applied as therapeutic agents for the treatment of cardiovascular diseases. Identification of novel strategies for miRNA/siRNA therapy requires a comprehensive understanding of the underlying mechanisms. Emerging data suggest that small RNAs are transferred between cells via gap junctions and provoke gene regulatory effects in the recipient cell. To elucidate the role of miRNA/siRNA as signalling molecules, suitable tools are required that will allow the analysis of these small RNAs at the cellular level...
September 2016: Journal of Molecular and Cellular Cardiology
Shuai Hou, Ming-Ming Zhao, Ping-Ping Shen, Xiu-Ping Liu, Yuan Sun, Jia-Chun Feng
This study investigated the neuroprotective effect of salvianolic acids (SA) against ischemia/reperfusion (I/R) injury, and explored whether the neuroprotection was dependent on mitochondrial connexin43 (mtCx43) via the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway. In vitro, we measured astrocyte apoptosis, mitochondrial membrane potential, and also evaluated the morphology of astrocyte mitochondria with transmission electron microscopy. In vivo, we determined the cerebral infarction volume and measured superoxide dismutase (SOD) activity and malondialdehyde (MDA) content...
2016: International Journal of Molecular Sciences
Gang Liu, Gaobin Luo, Zhandong Bo, Xiaonan Liang, Jie Huang, Donghui Li
Connexin(Cx)43 and microRNA(miR)-206 play an important role in osteogenesis. However, their role in steroid-induced femoral head osteonecrosis (SANFH) is still ambiguous. The present study aimed to establish a rabbit model and investigate osteogenesis in steroid-induced femoral head osteonecrosis occurring via Cx43/miR-206 and the changes of Wnt/β-catenin signal pathway-related proteins. A total of 72 adult New Zealand white rabbits were divided randomly into a model group (Group A) and a control group (Group B) of 36 rabbits each...
August 2016: Experimental and Molecular Pathology
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