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Masaki Murata, Makoto Osanai, Akira Takasawa, Kumi Takasawa, Tomoyuki Aoyama, Yuka Kawada, Akihiro Yamamoto, Yusuke Ono, Yutaro Hiratsuka, Takashi Kojima, Norimasa Sawada
Apical and basolateral cell membranes are separated by tight junctions (TJs). Microvilli are limited to the apical cell membrane. TJs and microvilli are the landmarks for epithelial cell polarity. However, the direct relationship between TJ proteins (TJPs) and the components of microvilli remains unclear. In this study, we investigated whether occludin, which is considered to be a functional TJP, is involved in microvillus formation. In occludin knockout mouse hepatic cells (OcKO cells), the microvillus density was less than that in wild-type (WT) cells and the length of microvilli was short...
March 16, 2018: Experimental Cell Research
Jun Wang, JinXin Lu, XiaoWei Xie, Jia Xiong, Ningning Huang, Hongkui Wei, Siwen Jiang, Jian Peng
Impaired epithelial barrier function disrupts immune homeostasis and increases inflammation in intestines, leading to many intestinal diseases. The blend of organic acids (OAs) and medium chain fatty acids (MCFAs) has been shown to have synergistic bactericidal effect. In this study, we demonstrated that two blends of OAs and MCFAs (OM1 and OM2) could prevent the inflammatory response and intestinal barrier dysfunction in enterohemorrhagic Escherichia coli (EHEC)-infected mice. Treatments of OM1 and OM2 significantly reduced the body weight loss and production of IL-6 and TNF-α induced by EHEC...
March 16, 2018: International Immunopharmacology
Yu Wu, Ze-Yang Ding, Guan-Nan Jin, Yi-Xiao Xiong, Bin Yu, Yi-Min Sun, Wei Wang, Hui-Fang Liang, Bixiang Zhang, Xiao-Ping Chen
Hepatic progenitor cells (HPCs) are a subpopulation of cells which was usually expanded in chronic liver injury and are contributed to liver regeneration through differentiating into hepatocytes and cholangiocytes. Epithelial-mesenchymal transition is a dynamic process which is important for the progression of liver fibrosis and cancer initiation. This study demonstrated that LE/6 and WB-F344 cells, both of which were HPC derived cell lines, were undergoing partial epithelial-mesenchymal transition states, which was indicated by the co-expression of epithelial markers (E-cadherin and zona occludin 1), and mesenchymal markers (vimentin, fibronectin, collagen 1and α-SMA)...
March 12, 2018: Biochimie
Yasmine Baktash, Anisha Madhav, Kelly E Coller, Glenn Randall
Hepatitis C virus (HCV) enters hepatocytes via various entry factors, including scavenger receptor BI (SR-B1), cluster of differentiation 81 (CD81), epidermal growth factor receptor (EGFR), claudin-1 (CLDN1), and occludin (OCLN). As CLDN1 and OCLN are not readily accessible due to their tight junctional localization, HCV likely accesses them by either disrupting cellular polarity or migrating to the tight junction. In this study, we image HCV entry into a three-dimensional polarized hepatoma system and reveal that the virus sequentially engages these entry factors through actin-dependent mechanisms...
March 14, 2018: Cell Host & Microbe
Yingying Liu, Yudiao Huang, Yueyue Xu, Peng Qu, Minghua Wang
Increased transendothelial permeability and subsequent blood-brain barrier damage play a key role in the pathological progression of human brain ischemia and secondary reperfusion. Memantine is a licensed drug providing clinically relevant efficacy in patients with Alzheimer's disease. However, little information is known regarding its effects on brain endothelial permeability. In this study, we investigated the effects of memantine on endothelial permeability and the underlying mechanisms in an ischemia-reperfusion (I/R) injury model in primary human brain microvascular endothelial cells...
March 15, 2018: IUBMB Life
Vandana Sekhar, Teresa Pollicino, Giacomo Diaz, Ronald E Engle, Farah Alayli, Marta Melis, Juraj Kabat, Ashley Tice, Anna Pomerenke, Nihal Altan-Bonnet, Fausto Zamboni, Paolo Lusso, Suzanne U Emerson, Patrizia Farci
Entry of hepatitis C virus (HCV) into hepatocytes is a complex process that involves numerous cellular factors, including the scavenger receptor class B type 1 (SR-B1), the tetraspanin CD81, and the tight junction (TJ) proteins claudin-1 (CLDN1) and occludin (OCLN). Despite expression of all known HCV-entry factors, in vitro models based on hepatoma cell lines do not fully reproduce the in vivo susceptibility of liver cells to primary HCV isolates, implying the existence of additional host factors which are critical for HCV entry and/or replication...
March 14, 2018: PLoS Pathogens
Xiu-Ting Yu, Yi-Fei Xu, Yan-Feng Huang, Chang Qu, Lie-Qiang Xu, Zi-Ren Su, Hui-Fang Zeng, Lin Zheng, Tie-Gang Yi, Hui-Lin Li, Jian-Ping Chen, Xiao-Jun Zhang
Ulcerative colitis (UC) is a chronic relapsing disease without satisfactory treatments, in which intestinal inflammation and disrupted intestinal epithelial barrier are two main pathogeneses triggering UC. Berberrubine (BB) is deemed as one of the major active metabolite of berberine (BBR), a naturally-occurring isoquinoline alkaloid with appreciable anti-UC effect. This study aimed to comparatively investigate the therapeutic effects of BB and BBR on dextran sodium sulfate (DSS)-induced mouse colitis model, and explore the potential underlying mechanism...
2018: PloS One
Dong-Yan Zhao, Wen-Xue Zhang, Qing-Qing Qi, Xin Long, Xia Li, Yan-Bo Yu, Xiu-Li Zuo
We aimed to investigate the effects of brain-derived neurotrophic factor (BDNF) on apoptosis of intestinal epithelial cells (IECs) and alterations of intestinal barrier integrity using BDNF knock-out mice model. Colonic tissues from BDNF(+/+) mice and BDNF(+/-) mice were prepared for this study. The integrity of colonic mucosa was evaluated by measuring trans-mucosa electrical resistance and tissue conductance in Ussing chamber. The colonic epithelial structure was analyzed by transmission electron microscopy...
March 12, 2018: Physiological Research
Kelly M DeMars, Austin O McCrea, David M Siwarski, Brian D Sanz, Changjun Yang, Eduardo Candelario-Jalil
Ischemic stroke occurs when a clot forms in the brain vasculature that starves downstream tissue of oxygen and nutrients resulting in cell death. The tissue immediately downstream of the blockage, the core, dies within minutes, but the surrounding tissue, the penumbra is potentially salvageable. Prostaglandin E2 binds to four different G-protein coupled membrane receptors EP1-EP4 mediating different and sometimes opposing responses. Pharmacological activation of the EP4 receptor has already been established as neuroprotective in stroke, but the mechanism(s) of protection are not well-characterized...
2018: Frontiers in Neuroscience
Sung Gil Ha, Mythili Dileepan, Xiao Na Ge, Bit Na Kang, Yana G Greenberg, Amrita Rao, Girija Muralidhar, Lali Medina-Kauwe, Michael A Thompson, Christina M Pabelick, Scott M O'Grady, Savita P Rao, P Sriramarao
BACKGROUND: Altered epithelial physical and functional barrier properties along with Th1/Th2 immune dysregulation are features of allergic asthma. Regulation of junction proteins to improve barrier function of airway epithelial cells has the potential for alleviation of allergic airway inflammation. OBJECTIVE: To determine the immunomodulatory effect of knob protein of the adenoviral capsid on allergic asthma and investigate its mechanism of action on airway epithelial junction proteins and barrier function...
March 6, 2018: Journal of Allergy and Clinical Immunology
Edit Páyer, Judit Szabó-Papp, Lídia Ambrus, Attila Gábor Szöllősi, Mónika Andrási, Shabtay Dikstein, Lajos Kemény, István Juhász, Andrea Szegedi, Tamás Bíró, Attila Oláh
Polyols (e.g. glycerol, xylitol) are implicated as moisturizers of the skin and other epithelial tissues. However, we lack information about their exact cellular mechanisms and their effects on the gene expression profiles. Therefore, in this study, we aimed at investigating the effects of glycerol and xylitol on human epidermal keratinocytes. The polyols (identical osmolarities; xylitol: 0.0045%-0.45%; glycerol: 0.0027%-0.27%) did not alter cellular viability or intracellular calcium concentration. However, they exerted differential effects on the expression of certain genes and signalling pathways...
March 2018: Experimental Dermatology
Bin Zhang, Xiuhui Chen, Yao Lin, Shaoyu Wang, Qiufang Bao
Objective: The objective of the study was to investigate the expression of the tight junction protein occludin (encoded by OCLN gene) in human cervical cancer and its association with clinical features of patients. Materials and Methods: Sixty-one patients with cervical cancer were included in this study from June 30, 2015 to April 30, 2017. Immuno-histochemical assay was applied to examine the expression of occludin protein in 61 cervical cancer tissues and matched adjacent cancer normal tissues...
January 2018: Journal of Cancer Research and Therapeutics
Vinay Kumar, Joshua Mansfield, Rong Fan, Andrew MacLean, Jian Li, Mahesh Mohan
Intestinal epithelial barrier dysfunction is a well-known sequela of HIV/SIV infection that persists despite antiretroviral therapy. Although inflammation is a triggering factor, the underlying molecular mechanisms remain unknown. Emerging evidence suggests that epithelial barrier function is epigenetically regulated by inflammation-induced microRNAs (miRNAs). Accordingly, we profiled and characterized miRNA/mRNA expression exclusively in colonic epithelium and identified 46 differentially expressed miRNAs (20 upregulated and 26 downregulated) in chronically SIV-infected rhesus macaques ( Macaca mulatta )...
March 7, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Kwang-Soo Kim, Jiewan Kim, Nuri Oh, Mi-Young Kim, Kyung-Soon Park
Gata3 is a master regulator that drives mammary epithelial cell differentiation, and the suppression of GATA3 expression is associated with the development of aggressive breast cancer. However, the mechanism through which GATA3 loss drives cancer development is poorly understood. Previously, we reported that ELK3 suppression in MDA-MB-231 (ELK3 KD) resulted in the reprogramming of these cells from a basal to luminal subtype, which was associated with the induction of GATA3 expression, and that the ELK3-GATA3 axis orchestrated the metastatic characteristics of MDA-MB-231...
March 3, 2018: Biochemical and Biophysical Research Communications
C Wasén, M Ekstrand, M Levin, D Giglio
PURPOSE: Epidermal growth factor receptor (EGFr)-targeted therapy may be used in subgroups of patients with urinary bladder cancer. Here we assessed the role of EGFr in urothelial proliferation and migration in a two- and three-dimensional cell culture system. METHODS: UROtsa cells derived from normal urothelium and malignant T24 cells were cultured in a Type I collagen gel. Proliferation and migration of urothelial cells, in the absence and presence of the EGFr inhibitor cetuximab, were assessed with a proliferation test (ATCC) and with the Axioplan 2 imaging microscope with a motorized stage (Carl Zeiss), respectively...
March 5, 2018: International Urology and Nephrology
Dacheng Wu, Keyan Wu, Qingtian Zhu, Weiming Xiao, Qing Shan, Zhigang Yan, Jian Wu, Bin Deng, Yan Xue, Weijuan Gong, Guotao Lu, Yanbing Ding
Formononetin is a kind of isoflavone compound and has been reported to possess anti-inflammatory properties. In this present study, we aimed to explore the protective effects of formononetin on dextran sulfate sodium- (DSS-) induced acute colitis. By intraperitoneal injection of formononetin in mice, the disease severity of colitis was attenuated in a dose-dependent manner, mainly manifesting as relieved clinical symptoms of colitis, mitigated colonic epithelial cell injury, and upregulations of colonic tight junction proteins levels (ZO-1, claudin-1, and occludin)...
2018: Mediators of Inflammation
Bhargavi Manda, Hina Mir, Ruchika Gangwar, Avtar S Meena, Shrunali Amin, Pradeep K Shukla, Kesha Dalal, Takuya Suzuki, Radha Krishna Rao
The apical junctional complex (AJC), which includes tight junction (TJ) and adherens junction (AJ) determine the epithelial polarity, cell-cell adhesion and permeability barrier. An intriguing characteristic of TJ is the dynamic nature of its multiprotein complex. Occludin is the most mobile TJ protein, but its significance in TJ dynamics is poorly understood. On the basis of phosphorylation sites we distinguished a sequence in the C-terminal domain of occludin as a regulatory motif (ORM). Deletion of ORM and expression of deletion mutant occludin in renal and intestinal epithelia reduced the mobility of occludin at the TJ...
March 5, 2018: Journal of Cell Science
Pilvi Laurikka, Katri Lindfors, Mikko Oittinen, Heini Huhtala, Teea Salmi, Marja-Leena Lähdeaho, Tuire Ilus, Markku Mäki, Katri Kaukinen, Kalle Kurppa
GOALS: The aim of this study was to investigate the role of dietary factors, distinct small-bowel mucosal immune cell types, and epithelial integrity in the perpetuation of gastrointestinal symptoms in treated celiac disease patients. BACKGROUND: For unexplained reasons, many celiac disease patients suffer from persistent symptoms, despite a strict gluten-free diet (GFD) and recovered intestinal mucosa. STUDY: We compared clinical and serological data and mucosal recovery in 22 asymptomatic and 25 symptomatic celiac patients on a long-term GFD...
March 2, 2018: Journal of Clinical Gastroenterology
Shuyuan Shen, Hai Yu, Xiaobai Liu, Yunhui Liu, Jian Zheng, Ping Wang, Wei Gong, Jiajia Chen, Lini Zhao, Yixue Xue
The blood-tumor barrier (BTB) restricts the efficient delivery of anti-glioma drugs to cranial glioma tissues. Increased BTB permeability may allow greater delivery of the therapeutic agents. Increasing evidence has revealed that PIWI proteins and PIWI-interacting RNAs (piRNAs) play an important role in tumor progression. However, whether PIWI proteins and piRNAs regulate BTB permeability remains unclear. In the present study, we demonstrated that the PIWIL1/piRNA-DQ593109 (piR-DQ593109) complex was the predominant regulator of BTB permeability...
March 2, 2018: Molecular Therapy. Nucleic Acids
Zhuo-Qiong Li, Ze-Yu Cao, Liang Cao, Zhi-Peng Ke, Zhen-Zhong Wang, Wei Xiao
The left middle cerebral artery occlusion (MCAO) model was made by inserting the nylon thread plug into the internal carotid artery. The behavioral score, cerebral infarction area, brain water content, ethidium bromide (EB) spillover, coagulation four indices, occludin and MMP-9 expression in brain tissues were detected after 14 days of administration, to investigate whether the protective effect of ginkgo diterpene lactone meglumine injection (GDLMI) which had obvious protective effect on cerebral ischemic injury in the previous experiment was related to reducing the permeability of the blood-brain barrier (BBB) and reducing the risk of bleeding, and to explore its possible mechanism of action...
December 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
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