Journal of epithelial biology & pharmacology最新文献

{"title":"Role of Airway Epithelial Cells in Development of Chronic Obstructive Pulmonary Disease","authors":"L. Ye, Xiangdong Wang, M. Jin","doi":"10.2174/1875044300902010044","DOIUrl":"https://doi.org/10.2174/1875044300902010044","url":null,"abstract":"Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation of peripheral airways that is not fully reversible. COPD is associated with airway remodeling, which thickens the airway walls and narrows the air- way as a result. Exposure to cigarette smoke is the major risk factor for this condition. Pathogens including viruses and bacteria may induce COPD exacerbations. Now there is more evidence to suggest a significant relationship between air- way epithelial cells and the pathogenesis of COPD. Airway epithelial cells make up an efficient barrier against pathogens and aggressive molecules. However, after exposure to cigarette smoke and pathogens, epithelial cells are stimulated to re- lease a variety of pro-inflammatory mediators, including chemokines, cytokines, and growth factors through signaling pathways. These mediators recruit or stimulate other types of cells to induce an increased inflammatory response, produc- tion of mucus, and finally result in airway remodeling. After epithelium injury, epithelial cells participate in the process of repair and regeneration to maintain the epithelial integrity. A better understanding of the role of airway epithelial cells in COPD may be valuable to provide a basis for new therapeutic strategies.","PeriodicalId":88010,"journal":{"name":"Journal of epithelial biology & pharmacology","volume":"2 1","pages":"44-50"},"PeriodicalIF":0.0,"publicationDate":"2009-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68109911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of Renal LAT2 and 4F2hc Expression by Aldosterone","authors":"M. Pinho, J. Amaral, V. Pinto, M. Serrão, P. Soares-da-Silva","doi":"10.2174/1875044300902010036","DOIUrl":"https://doi.org/10.2174/1875044300902010036","url":null,"abstract":"In the spontaneous hypertensive rat, overexpression of the renal Na + -independent L-amino acid transporter LAT2 is organ specific, precedes the onset of hypertension, correlates negatively with plasma aldosterone, and parallels the enhanced ability to take up L-DOPA and form renal dopamine. The present study evaluated the role of aldosterone on transcript and protein abundance of Na + -independent and Na + -dependent amino acid transporters. Na + -independent het- erodimeric amino acid transporters LAT1/4F2hc, LAT2/4F2hc and a Na + -dependent transporter ASCT2 transcript and protein abundance was determined in the renal cortex of normotensive Wistar rats chronically treated with aldosterone (1.5 mg), spironolactone (200 mg) or aldosterone plus spironolactone. Aldosterone significantly increased renal cortical LAT2 mRNA levels (45 % increase), with no changes in LAT1, 4F2hc and ASCT2 transcript levels. The effect of aldos- terone upon LAT2 mRNA levels was completely prevented by spironolactone. At the protein level, aldosterone treatment did not significantly affect LAT1 and LAT2 expression, but markedly reduced (51 % decrease) the abundance of 4F2hc and the urinary excretion of dopamine and DOPAC. The effect of aldosterone upon 4F2hc protein abundance was not re- versed by spironolactone. Increases in renal LAT2 transcript during chronic treatment with aldosterone occur through a spironolactone-sensitive genomic mechanism. This effect parallels with a decrease in LAT2 functionality, resulting from decreases in 4F2hc protein abundance, which appears to be either a non-genomic effect or an indirect effect of aldoster- one. The decrease in LAT2 functionality by aldosterone correlates well with the reduction in urinary dopamine.","PeriodicalId":88010,"journal":{"name":"Journal of epithelial biology & pharmacology","volume":"2 1","pages":"36-43"},"PeriodicalIF":0.0,"publicationDate":"2009-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68109872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Alveolar Epithelium and Pulmonary Fibrosis","authors":"Huiping Li","doi":"10.2174/1875044300902010030","DOIUrl":"https://doi.org/10.2174/1875044300902010030","url":null,"abstract":"Idiopathic interstitial pneumonias (IIPs) are a heterogeneous group of diffuse pulmonary parenchymal diseases that are comprised of seven distinct clinical and pathological entities. Idiopathic pulmonary fibrosis (IPF) and cryptogenic organizing pneumonia (COP) represent two of the most prevalent members of the disease group with major differences in their pathogenesis, clinical course and prognosis. IPF is a refractory and lethal IIP characterized by fibroblast prolifera- tion, deposition of extracellular matrix (ECM) and progressive lung scarring. The incidence of IPF is estimated at 15 to 40 cases per 100,000 per year, and the mean survival from the time of diagnosis is 3 to 5 years regardless of treatment. While its pathogenesis is incompletely understood, the currently accepted paradigm proposes that injury of the alveolar epithe- lium is followed by a burst of pro-inflammatory and fibroproliferative mediators that invoke responses associated with dysregulated repair of the damaged alveolar epithelium. Recently, there have been studies suggesting that the activation of the alveolar epithelial cells (AECs) may play an active role in the pathogenesis of pulmonary fibrosis. Here, we review the advances in recent studies on the role of the alveolar epithelium in pulmonary fibrosis. AECS: A BRIEF OVERVIEW OF STRUCTURE AND PHYSIOLOGICAL FUNCTIONS Two types of AECs populate the alveolar epithelium in normal adult lungs, alveolar epithelial type I (AT I) and al- veolar epithelial type II (AT II) cells. AT I pneumocytes comprise 40% of the AECs and cover 90% of the internal surface area of the lung. AT I cells are highly attenuated and form an interface with pulmonary capillaries that are inti- mately involved in gas exchange. These cells also take part in peptide and amino acid transportation across the lung by pinocytosis and transporter-mediated transport (1). Recently, AT I cells have been shown to be also important in the trans- portation of water and sodium across the lung (2, 3). AT II cells, on the other hand, AT II cells make up 16% of the parenchymal cells in the lung and account for only 5% of the alveolar surface. These cells are cuboidal cells that are situated between AT I cells and they contain characteristic lamellar bodies and apical microvilli. AT II cells synthesize, store and secrete the pulmonary surfactant (PS), which con- sists of lipids and their associated proteins and whose func- tion is to reduce the surface tension of the lung alveolus and prevent it from collapse or overdistension with respiration. AT II cells also regulate alveolar fluid balance in normal lungs and during the resolution of pulmonary edema (4) and the pathogenesis of acute lung injury with pulmonary edema is associated with an insufficient number of AT II cells and transportation of water into the lung alveolus. Recently, AT II cells have been shown to synthesize and secrete immuno- modulatory proteins important for host defense, including surfactant prot","PeriodicalId":88010,"journal":{"name":"Journal of epithelial biology & pharmacology","volume":"2 1","pages":"30-35"},"PeriodicalIF":0.0,"publicationDate":"2009-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68109861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gradient Perfusion Culture - Simulating a Tissue-Specific Environment for Epithelia in Biomedicine","authors":"W. Minuth, L. Denk, Anne Roessger","doi":"10.2174/1875044300902010001","DOIUrl":"https://doi.org/10.2174/1875044300902010001","url":null,"abstract":"Epithelia act in the organism as biological barriers. All of them are exposed to different environments at the luminal and basal side. To simulate such a tissue-specific situation Minusheet ® gradient perfusion culture was developed. For pharmaceutical research, biomaterial testing and tissue engineering epithelial cells are cultured on individually se- lected supports (1). Growing epithelia are stabilized within a tissue carrier (2). Long term culture is performed in a gradi- ent perfusion container (3). To expose epithelia to a tissue-specific environment fresh media of different composition are transported parallel to the luminal and basal compartment of the gradient container. During culture leakage, edge damage and pressure differences have to be avoided. Harvest of intact epithelia is promoted by the use of biocompatible supports and innovative equipment such as transport of oxygen-rich and gas bubble-free medium. Actual literature demonstrates that gradient perfusion culture is an effective method to investigate barrier functions under realistic conditions. Examples of application comprise renal epithelia, retina, blood-air barrier, blood-brain barrier including aspects of tissue-specific development and regeneration.","PeriodicalId":88010,"journal":{"name":"Journal of epithelial biology & pharmacology","volume":"2 1","pages":"1-13"},"PeriodicalIF":0.0,"publicationDate":"2009-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68110131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tobacco Smoke Activates Protein Association and Tyrosine Phosphorylation of the GPI-Transamidase Complex Subunits in Human Cancers","authors":"Yiping Huang, J. Nagpal, B. Trink, E. Ratovitski","doi":"10.2174/1875044300902010014","DOIUrl":"https://doi.org/10.2174/1875044300902010014","url":null,"abstract":"We previously found that the protein subunits of GPI-transamidase complex (e.g. PIG-U, PIG-T and GPAA1) play critical roles of oncogenes in human bladder and breast cancers manifesting their activities through signaling mecha- nisms that involve urokinase receptor/Stat3 and paxillin pathways. We report here that cigarette smoke extract (CSE) en- hanced colony formation and invasiveness of certain human cancer cells (e.g. head and neck, bladder or breast). We found that CSE induced the complex formation between PIG-U, PIG-T and GPAA1 proteins and also the association between GPAA1 and EGFR in cancer cells. We observed that inhibitors of EGFR tyrosine kinase, Gefitinib or Erlotinib, modu- lated tyrosine phosphorylation of PIG-U and PIG-T induced by CSE. We also found that EGFR tyrosine kinase inhibitors and siRNA silencing of PIG-U, PIG-T or GPAA1 modulated the CSE-induced increase in colony formation and invasive- ness of human bladder cancer cells. We suggest that the novel mechanism overlapping the oncogenic potential of PIG-U, PIG-T and GPAA1 implicates EGFR tyrosine phosphorylation of PIG-U or PIG-T and subsequent paxillin phosphoryla- tion.","PeriodicalId":88010,"journal":{"name":"Journal of epithelial biology & pharmacology","volume":"2 1","pages":"14-22"},"PeriodicalIF":0.0,"publicationDate":"2009-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68109829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Glucosylceramide Synthase Inhibitor Prevents the Cytotoxic Effects of Shiga Toxin-2 on Human Renal Tubular Epithelial Cells","authors":"C. Silberstein, D. Copeland, W. Chiang, H. Repetto, C. Ibarra","doi":"10.2174/1875044300801010071","DOIUrl":"https://doi.org/10.2174/1875044300801010071","url":null,"abstract":"Shiga toxin-2 binds to the globotriaosyl-ceramide receptor on the plasma membrane of target cells. The high level expression of this receptor in renal epithelial cells may account, at least in part, for acute renal failure observed in children with hemolytic uremic syndrome. The cytotoxic effect of Shiga toxin-2 was assayed on primary cultures of hu- man renal tubular epithelial cells treated with a new specific inhibitor of glucosylceramide synthase (C-9), the rate- limiting first step in the glycosphingolipid biosynthetic pathway. The treatment of the cells with 1-5 �M C-9 for at least 24 h significantly neutralized the action of 1 ng/ml Shiga toxin-2 on cell viability. The expression levels of globotriaosyl- ceramide significantly decreased when cells were incubated with 1 �M C-9 for 48 h. We propose here that prevention of globotriaosyl-ceramide synthesis by the C-9 could be a novel substrate inhibition therapy to neutralize Shiga toxin-2 ac- tion in renal epithelial cells.","PeriodicalId":88010,"journal":{"name":"Journal of epithelial biology & pharmacology","volume":"1 1","pages":"71-75"},"PeriodicalIF":0.0,"publicationDate":"2009-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68109734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Role of CC Chemokines and their Receptors in the Development of Respiratory Diseases","authors":"L. Tong, Yaoli Wang, J. Bi, Dong Yang, C. Bai, Xiang-dong Wang","doi":"10.2174/1875044300801010076","DOIUrl":"https://doi.org/10.2174/1875044300801010076","url":null,"abstract":"Increasing evidence suggests that the chemokine system coordinates leukocyte migration in immunity and in- flammation, involving in the pathogenesis of many pulmonary diseases. Chemokines are small proteins which interact with specific receptors to exert their chemotactic functions for inflammatory cells and constitutive cells. Among the com- plex system, CC chemokine receptors (CCRs) represent a subfamily of chemokine receptor, which is considered to play an important role in the pathogenesis of diseases characterized by disordered inflammation and immunity, among which some respiratory diseases, such as asthma, chronic obstructive pulmonary disease, acute lung injury, comprise one impor- tant part. The present paper reviewed the research of possible relationship and progress between this system and human lung diseases. Chemokines and their receptors are essential components of Th1- and Th2-mediated responses via the re- cruitment of lymphocytes and macrophages. The local expression of homeostatic chemokines in pulmonary also plays an important role in protective immune responses. Thus, it is important to understand the potential role of CCRs in respira- tory diseases and it may provide exciting new targets for therapeutic intervention.","PeriodicalId":88010,"journal":{"name":"Journal of epithelial biology & pharmacology","volume":"1 1","pages":"76-84"},"PeriodicalIF":0.0,"publicationDate":"2009-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68109791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Candesartan Differentially Regulates Epithelial Sodium Channel in Cortex Versus Medulla of Streptozotocin-Induced Diabetic Rats.","authors":"Janet D Klein, Arjun Rash, Jeff M Sands, Carolyn M Ecelbarger, Swasti Tiwari","doi":"10.2174/1875044300902010023","DOIUrl":"10.2174/1875044300902010023","url":null,"abstract":"<p><p>Diabetes is associated with an activated renal renin-angiotensin-aldosterone system (RAAS) and it was shown that streptozotocin (STZ)-induced diabetic rats had increased whole kidney protein levels of the epithelial sodium channel subunits (α-, β- and γ-ENaC). However, the role of the RAAS on the regional, i.e., cortical versus medullary, regulation of ENaC is unclear. Male Sprague-Dawley rats were injected with STZ (intravenous, 65 mg/kg·bw, n=12/group). After 14 days, half of them received drinking water with candesartan (2 mg/kg·bw/day), an angiotensin-II type-1 receptor (AT1R) antagonist, for one week. In the medulla, i.e., inner stripe of the outer medulla (ISOM), base and/or tip of the inner medulla, immunoblotting revealed increased protein abundances of α1 Na-K-ATPase and ENaC subunits with diabetes (200-600% of controls), which were not reversed by candesartan. In fact, candesartan increased all ENaC subunits and α1 Na-K-ATPase in the ISOM and/or base in control rats. In contrast, in the cortex, diabetes did not increase these proteins. However, candesartan reduced cortical β- and γ-ENaC regardless of diabetic state. In summary, diabetes-induced increases in ENaC were seen preferentially in the medulla. These changes appeared to be due to a mechanism clearly distinct from AT1R activation, because they were not abolished by candesartan. In fact, candesartan treatment tended to increase some of these medullary proteins, perhaps in compensation for increased NaCl load. In contrast, cortical β- and γ-ENaC were reduced by candesartan regardless of diabetic state suggesting their regulation by AT1R at this site; however this did not appear to be a site of diabetes-induced ENaC up-regulation.</p>","PeriodicalId":88010,"journal":{"name":"Journal of epithelial biology & pharmacology","volume":"2 7","pages":"23"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819702/pdf/nihms124028.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28709752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelin-1 Induces Expression of Connective Tissue Growth Factor in Bronchial Epithelial Cells","authors":"A. Dosanjh","doi":"10.2174/1875044300801010068","DOIUrl":"https://doi.org/10.2174/1875044300801010068","url":null,"abstract":"Endothelin-1 (ET-1) is a potent vaso and bronchoconstrictor. We have previously shown that in the presence of ET-1 bronchial epithelial cells migrate more slowly. Connective tissue growth factor (CTGF) is a cysteine rich secreted protein and regulates fibrosis. In addition, we have previously shown that CTGF is expressed in airway epithelial cells under the conditions of stress starvation. The aim of this study was to describe the effect of ET-1 on CTGF expression, us- ing a lung epithelial-fibroblast co-culture system. Bronchial epithelial cells (BEC) were grown and stimulated with ET-1, 100ng/ml of media, for 24 hours. At 0, 4 and 24 hours, total RNA was isolated. Reverse transcription PCR was performed and CTGF transcripts were semi-quantified. In addition, BEC were grown in co-culture, in the presence of human lung fi- broblasts (FB). The same experiment was conducted for FB grown in the presence or absence of ET-1. Control cells were grown only in the basal media. At both time points, following exposure to ET-1, BEC expressed more CTGF as compared to control. Cells in co-culture with FB, expressed no CTGF at 4 hours, and detectable CTGF at 24 hours. CTGF was de- tected at all time points for FB in both control and stimulated cells. ET-1 induces expression of CTGF in BEC as com- pared to control. ET-1 may be an important regulator of CTGF expression in the airway. Lung fibroblasts may secrete epithelial cell regulatory factors, controlling the expression of CTGF in the presence of ET-1.","PeriodicalId":88010,"journal":{"name":"Journal of epithelial biology & pharmacology","volume":"1 1","pages":"68-70"},"PeriodicalIF":0.0,"publicationDate":"2008-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68110265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tear Film and Ocular Surface Surfactants","authors":"L. Bräuer, F. Paulsen","doi":"10.2174/1875044300801010062","DOIUrl":"https://doi.org/10.2174/1875044300801010062","url":null,"abstract":"The hydrophobic surfactant proteins B (SP-B) and C (SP-C) are tightly bound to phospholipids. These proteins play important roles in maintaining the surface tension-lowering properties of pulmonary surfactant. Surfactant protein A (SP-A) and D (SP-D) are extremely hydrophilic and are thought to have a role in recycling surfactant and especially in improving host defense in the lung. Moreover, SP-A supports the hydrophobic surfactant proteins during surfactant sub- type assembly and inhibits secretion of lamellar bodies into the alveolar space. During recent years surfactant proteins have also been detected at locations outside the lung such as the lacrimal apparatus. In this review, the latest information regarding SP function and regulation in the human lacrimal system, the tear film and the ocular surface is summarized with regard to mucous epithelial integrity, rheological and antimicrobial properties of the tear film, tear outflow, certain disease states and possible therapeutic perspectives.","PeriodicalId":88010,"journal":{"name":"Journal of epithelial biology & pharmacology","volume":"22 1","pages":"62-67"},"PeriodicalIF":0.0,"publicationDate":"2008-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68110217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}