{"title":"Mucin Glycan Expression is Individual-Specific and Governed by the In Situ Microenvironment","authors":"A. Slomiany, B. Slomiany","doi":"10.2174/1875044300801010054","DOIUrl":"https://doi.org/10.2174/1875044300801010054","url":null,"abstract":"Mucin glycosylation and individual susceptibility to disease is linked to the in situ microenvironment that de- termines features of the individual- and disease-specific glycans. In tissue culture paradigm, the in situ environment is not recreated and the synthesis of signature glycans vanishes. To evaluate the impact of the in situ-specific gastric epithelial environment on mucin glycan synthesis we investigated gastric mucin collected from 36 individual rats subjected to the same conditions and diet. The secretion collected during 3 hours of gastric perfusion contained from 67.7 to 1096.6 nmol mucin glycans and from 42.0 to 245.8 nmol glycosphingolipids (GSL). We identified four groups, each consisting of 6 animals, that contained O-glycans interacting with apical epithelial mucin receptor comprised of N-acetylgalactosamine (GalNAc), galactose (Gal), N-acetylglucosamine (GlcNAc) and fucose (Fuc ) in the ratio of 1:2:2:1, 1:2:3:1, 1:3:2:1, and 1:4:2:1. The remaining 10 rats produced glycans containing GalNAc, Gal, GlcNAc, Fuc in ratio 1:1:1:1, partially fucosy- lated glycans, and Fuc-free glycans consisting of GalNAc:Gal:GlcNAc in ratio of 1:4:2. The data support our hypothesis that individual-specific-gastric epithelial environment and individual-specific metabolome provide final imprint on the quantity, composition, and termination of mucin O-glycans.","PeriodicalId":88010,"journal":{"name":"Journal of epithelial biology & pharmacology","volume":"1 1","pages":"54-61"},"PeriodicalIF":0.0,"publicationDate":"2008-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68110210","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}
A. Kareddula, E. Zachariah, D. Notterman, M. Reiss
{"title":"Transforming Growth Factor-β Signaling Strength Determines Target Gene Expression Profile in Human Keratinocytes","authors":"A. Kareddula, E. Zachariah, D. Notterman, M. Reiss","doi":"10.2174/1875044300801010040","DOIUrl":"https://doi.org/10.2174/1875044300801010040","url":null,"abstract":"Transforming Growth Factor(TGF ) maintains keratinocyte homeostasis, and induces epithelial-tomesenchymal transition (EMT) in response to tissue injury. To investigate how these two TGF responses might become uncoupled during malignant transformation, we examined the TGF -regulated gene expression programs and cellular responses in human keratinocytes as a function of TGF type I receptor (T R-I) kinase activity and TGF level. The TGF mediated homeostatic gene response program and cellular growth arrest were extremely sensitive to a reduction in receptor kinase activity, while much stronger inhibition of TGF receptor activity was needed to inhibit the tissue injury response gene expression program and EMT. Both endogenous TGF and high exogenous levels of TGF induced the homeostatic response, while only high levels of TGF induced EMT. These results suggest that a reduction in receptor signaling activity may be sufficient for keratinocytes to escape from TGF ’s tumor suppressor function, while higher levels of TGF associated with tumor progression are pro-invasive/metastatic. These findings have important implications for the optimal use of TGF /Smad signaling antagonists as anti-cancer therapeutics.","PeriodicalId":88010,"journal":{"name":"Journal of epithelial biology & pharmacology","volume":"1 1","pages":"40-53"},"PeriodicalIF":0.0,"publicationDate":"2008-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68110120","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}
G. Seki, Hideomi Yamada, S. Horita, Masashi Suzuki, T. Sekine, T. Igarashi, T. Fujita
{"title":"Activation and Inactivation Mechanisms of Na-HCO3 Cotransporter NBC1","authors":"G. Seki, Hideomi Yamada, S. Horita, Masashi Suzuki, T. Sekine, T. Igarashi, T. Fujita","doi":"10.2174/1875044300801010035","DOIUrl":"https://doi.org/10.2174/1875044300801010035","url":null,"abstract":"The electrogenic Na + -HCO3 - cotransporter NBC1, also known as NBCe1, is expressed in several tissues such as kidney, pancreas, eye, and brain. NBC1 has three variants, which may mediate different physiological functions. Inacti- vating mutations in NBC1 result in proximal renal tubular acidosis associated with ocular abnormalities. Functional analysis suggests that at least 50% reduction in NBC1 activity is required to induce severe acidemia invariably associated with stunted growth. Some mutations in the NBC1 gene may also induce trafficking abnormalities. On the other hand, the variant-specific N-terminal regions seem to play an essential role in the full activation of NBC1. This review will focus on the recent progress in physiology and pathophysiology of NBC1.","PeriodicalId":88010,"journal":{"name":"Journal of epithelial biology & pharmacology","volume":"1 1","pages":"35-39"},"PeriodicalIF":0.0,"publicationDate":"2008-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68110113","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":"Mineralocorticoid Receptor, Heat Shock Proteins and Immunophilins Par- ticipate in the Transmission of the Tubulogenic Signal of Aldosterone","authors":"W. Minuth, A. Blattmann, L. Denk, H. Castrop","doi":"10.2174/1875044300801010024","DOIUrl":"https://doi.org/10.2174/1875044300801010024","url":null,"abstract":"Aldosterone exhibits a tubulogenic activity on renal stem/progenitor cells. Little information is available about the signaling between the mineralocorticoid receptor (MR) and the proteins in the cytoplasm. To obtain information, renal stem/progenitor cells from neonatal rabbit were cultured at the interface of an artificial polyester interstitium in a perfu- sion container for 13 days. Development was registered with Soybean Agglutinin (SBA). Microscopy revealed that treat- ment with aldosterone (1 x 10 -7 M) resulted in numerous SBA-labeled tubules. Interference with mineralocorticoid recep- tor (MR) and heat shock protein (hsp) 90 using geldanamycin (3,6 x 10 -6 M) or radicicol (1 x 10 -6 M) showed a lack of tu- bule development. Disturbing MR and hsp 70 with quercetin (2 x 10 -4 M) and KNK 437 (1 x 10 -4 M) generated SBA- labeled cell cluster but not structured tubules. Interference with MR and immunophilins by cyclosporin A (2 x 10 -6 M) and rapamycin (2,2 x 10 -9 M) did not influence the generation of numerous SBA-labeled tubules. In contrast, administration of FK 506 (2 x 10 -8 M) resulted in a lack of tubule development. Thus, the signal for development of tubules induced by al- dosterone is mediated by interaction of MR, hsp 90, hsp 70 and immunophilin FKBP 12.","PeriodicalId":88010,"journal":{"name":"Journal of epithelial biology & pharmacology","volume":"1 1","pages":"24-34"},"PeriodicalIF":0.0,"publicationDate":"2008-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68110025","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":"Epithelial Brush Border Proteomics and Associated Cell Dysfunction","authors":"Xiangdong Wang, K. Adler","doi":"10.2174/1875044300801010016","DOIUrl":"https://doi.org/10.2174/1875044300801010016","url":null,"abstract":"Functions and structures of epithelial cells vary, depending upon their locations in organs/tissues. Pathophysi- ological responses of epithelia are associated with challenges, severities, durations and diseases. Epithelial proteomics has been used to understand the role of these cells in the pathogenesis of several diseases, and has the potential to identify novel biomarkers for disease prognosis, diagnosis and therapies. Epithelial brush border membranes (BBMs) are involved in digestion, absorption, metabolism, and transport of nutrients and drugs, clearance of and defense against toxins, and ini- tiation of intracellular signaling and maintenance of cellular structural integrity. The present article review proteomic re- search on epithelial brush borders to understand the potential links among the function and disease associations of epithe- lial BBM proteomics. We found that the amount and functional ratio of epithelial cell BBM proteomic profiles obviously vary among species, cell locations, organ functions, research groups, and methodologies utilized. Many of these proteins may be identified and their functions elucidated, probably providing potential new markers for epithelial-associated dis- eases and potential therapeutic targets. There is still a great need for proteomic studies for analysis and comparisons of BBM protein profiles associated with normal physiological and pathophysiological states, organ function and dysfunction, and clinical health and disease.","PeriodicalId":88010,"journal":{"name":"Journal of epithelial biology & pharmacology","volume":"1 1","pages":"16-23"},"PeriodicalIF":0.0,"publicationDate":"2008-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68109934","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":"Interleukin-13 is Expressed in Mouse Kidney Allograft Rejection and Mediates Proliferation of Renal Tubular Epithelium In Vitro","authors":"R. Thuillier, O. Cheng, R. Mannon","doi":"10.2174/1875044300801010008","DOIUrl":"https://doi.org/10.2174/1875044300801010008","url":null,"abstract":"Kidney transplantation is the preferred therapy for kidney failure. The leading cause of graft loss is chronic al- lograft nephropathy (CAN). We hypothesize that Interleukin-13 (IL-13), protective against acute kidney graft rejection, is involved in CAN. In mouse kidney allografts, we observe after 2 weeks signs of interstitial inflammation progressing to vasculitis. By 6 weeks, CAN is manifest. IL-13 is overexpressed in allografts versus isografts (p<0.01) throughout the post-transplant course. Concomitantly, we detect markers of fibrogenesis and epithelial-mesenchymal transition. To ex- plore this phenomenon, kidney proximal tubular epithelial cells were cultured with IL-13. Within 6 hours, we show in- creased proliferation compared to untreated cells (p<0.01), occurring through activation of IL4R� /JAK3 and Stat6 and blocked by anti-IL-13 monoclonal antibody. This is the first report of IL-13 inducing a specific biological activity in kid- ney epithelial cells with a possible role in the damage control machinery, indicating its potential as a biomarker and thera- peutic target.","PeriodicalId":88010,"journal":{"name":"Journal of epithelial biology & pharmacology","volume":"1 1","pages":"8-15"},"PeriodicalIF":0.0,"publicationDate":"2008-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68109853","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":"Electrolyte and Fluid Transport in Mesothelial Cells.","authors":"Hong-Long Ji, Hong-Guang Nie","doi":"10.2174/1875044300801010001","DOIUrl":"10.2174/1875044300801010001","url":null,"abstract":"<p><p>Mesothelial cells are specialized epithelial cells, which line the pleural, pericardial, and peritoneal cavities. Accumulating evidence suggests that the monolayer of mesothelial cells is permeable to electrolyte and fluid, and thereby govern both fluid secretion and re-absorption in the serosal cavities. Disorders in these salt and fluid transport systems may be fundamental in the pathogenesis of pleural effusion, pericardial effusion, and ascites. In this review, we discuss the location, physiological function, and regulation of active transport (Na(+)-K(+)-ATPase) systems, cation and anion channels (Na(+), K(+), Cl(-), and Ca(2+) channels), antiport (exchangers) systems, and symport (co-transporters) systems, and water channels (aquaporins). These secretive and absorptive pathways across mesothelial monolayer cells for electrolytes and fluid may provide pivotal therapeutical targets for novel clinical intervention in edematous diseases of serous cavities.</p>","PeriodicalId":88010,"journal":{"name":"Journal of epithelial biology & pharmacology","volume":"1 ","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2629602/pdf/nihms47739.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27945976","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}