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Prostasin

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https://www.readbyqxmd.com/read/29438412/tissue-distribution-and-subcellular-localizations-determine-in-vivo-functional-relationship-among-prostasin-matriptase-hai-1-and-hai-2-in-human-skin
#1
Shiao-Pieng Lee, Chen-Yu Kao, Shun-Cheng Chang, Yi-Lin Chiu, Yen-Ju Chen, Ming-Hsing G Chen, Chun-Chia Chang, Yu-Wen Lin, Chien-Ping Chiang, Jehng-Kang Wang, Chen-Yong Lin, Michael D Johnson
The membrane-bound serine proteases prostasin and matriptase and the Kunitz-type protease inhibitors HAI-1 and HAI-2 are all expressed in human skin and may form a tightly regulated proteolysis network, contributing to skin pathophysiology. Evidence from other systems, however, suggests that the relationship between matriptase and prostasin and between the proteases and the inhibitors can be context-dependent. In this study the in vivo zymogen activation and protease inhibition status of matriptase and prostasin were investigated in the human skin...
2018: PloS One
https://www.readbyqxmd.com/read/29363322/albuminuria-in-kidney-transplant-recipients-is-associated-with-increased-urinary-serine-proteases-and-activation-of-the-epithelial-sodium-channel
#2
Gitte Rye Hinrichs, Jannie Solmunde Michelsen, Rikke Zachar, Ulla Glenert Friis, Per Svenningsen, Henrik Birn, Claus Bistrup, Boye L Jensen
Albuminuria predicts adverse renal outcome in kidney transplant recipients. The present study addressed the hypothesis that albuminuria is associated with increased urine serine proteases with the ability to activate the epithelial sodium channel (ENaC) and with greater extracellular volume and higher blood pressure. In a cross-sectional design, kidney transplant recipients with (n=18) and without (n=19) albuminuria were included for office blood pressure measurements, estimation of volume status by bioimpedance, and collection of spot urine and plasma samples...
January 24, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28915606/proteolytic-cleavages-in-the-extracellular-domain-of-receptor-tyrosine-kinases-by-membrane-associated-serine-proteases
#3
Li-Mei Chen, Karl X Chai
The epithelial extracellular membrane-associated serine proteases matriptase, hepsin, and prostasin are proteolytic modifying enzymes of the extracellular domain (ECD) of the epidermal growth factor receptor (EGFR). Matriptase also cleaves the ECD of the vascular endothelial growth factor receptor 2 (VEGFR2) and the angiopoietin receptor Tie2. In this study we tested the hypothesis that these serine proteases may cleave the ECD of additional receptor tyrosine kinases (RTKs). We co-expressed the proteases in an epithelial cell line with Her2, Her3, Her4, insulin receptor (INSR), insulin-like growth factor I receptor (IGF-1R), the platelet-derived growth factor receptors (PDGFRs) α and β, or nerve growth factor receptor A (TrkA)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28490634/inflammatory-cytokines-down-regulate-the-barrier-protective-prostasin-matriptase-proteolytic-cascade-early-in-experimental-colitis
#4
Marguerite S Buzza, Tierra A Johnson, Gregory D Conway, Erik W Martin, Subhradip Mukhopadhyay, Terez Shea-Donohue, Toni M Antalis
Compromised gastrointestinal barrier function is strongly associated with the progressive and destructive pathologies of the two main forms of irritable bowel disease (IBD), ulcerative colitis (UC), and Crohn's disease (CD). Matriptase is a membrane-anchored serine protease encoded by suppression of tumorigenicity-14 (ST14) gene, which is critical for epithelial barrier development and homeostasis. Matriptase barrier-protective activity is linked with the glycosylphosphatidylinositol (GPI)-anchored serine protease prostasin, which is a co-factor for matriptase zymogen activation...
June 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28454094/proteolytic-cleavages-in-the-extracellular-domain-of-receptor-tyrosine-kinases-by-membrane-associated-serine-proteases
#5
Li-Mei Chen, Karl X Chai
The epithelial extracellular membrane-associated serine proteases matriptase, hepsin, and prostasin are proteolytic modifying enzymes of the extracellular domain (ECD) of the epidermal growth factor receptor (EGFR). Matriptase also cleaves the ECD of the vascular endothelial growth factor receptor 2 (VEGFR2) and the angiopoietin receptor Tie2. In this study we tested the hypothesis that these serine proteases may cleave the ECD of additional receptor tyrosine kinases (RTKs). We co-expressed the proteases in an epithelial cell line with Her2, Her3, Her4, insulin receptor (INSR), insulin-like growth factor I receptor (IGF-1R), the platelet-derived growth factor receptors (PDGFRs) α and β, or nerve growth factor receptor A (TrkA)...
April 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28125689/selective-inhibition-of-prostasin-in-human-enterocytes-by-the-integral-membrane-kunitz-type-serine-protease-inhibitor-hai-2
#6
Frank Shiao, Li-Ching O Liu, Nanxi Huang, Ying-Jung J Lai, Robert J Barndt, Chun-Che Tseng, Jehng-Kang Wang, Bailing Jia, Michael D Johnson, Chen-Yong Lin
Mutations of hepatocyte growth factor activator inhibitor (HAI)-2 in humans cause sodium loss in the gastrointestinal (GI) tract in patients with syndromic congenital sodium diarrhea (SCSD). Aberrant regulation of HAI-2 target protease(s) was proposed as the cause of the disease. Here functional linkage of HAI-2 with two membrane-associated serine proteases, matriptase and prostasin was analyzed in Caco-2 cells and the human GI tract. Immunodepletion-immunoblot analysis showed that significant proportion of HAI-2 is in complex with activated prostasin but not matriptase...
2017: PloS One
https://www.readbyqxmd.com/read/27936035/natural-endogenous-human-matriptase-and-prostasin-undergo-zymogen-activation-via-independent-mechanisms-in-an-uncoupled-manner
#7
Hui Chen Su, Yan A Liang, Ying-Jung J Lai, Yi-Lin Chiu, Robert B Barndt, Frank Shiao, Hsiang-Hua D Chang, Dajun D Lu, Nanxi Huang, Chun-Che Tseng, Jehng-Kang Wang, Ming-Shyue Lee, Michael D Johnson, Shih-Ming Huang, Chen-Yong Lin
The membrane-associated serine proteases matriptase and prostasin are believed to function in close partnership. Their zymogen activation has been reported to be tightly coupled, either as a matriptase-initiated proteolytic cascade or through a mutually dependent mechanism involving the formation of a reciprocal zymogen activation complex. Here we show that this putative relationship may not apply in the context of human matriptase and prostasin. First, the tightly coupled proteolytic cascade between matriptase and prostasin might not occur when modest matriptase activation is induced by sphingosine 1-phospahte in human mammary epithelial cells...
2016: PloS One
https://www.readbyqxmd.com/read/27755216/altered-prostasin-cap1-prss8-expression-favors-inflammation-and-tissue-remodeling-in-dss-induced-colitis
#8
Anna Keppner, Sumedha Malsure, Antoine Nobile, Muriel Auberson, Olivier Bonny, Edith Hummler
BACKGROUND: Inflammatory bowel diseases (IBD) including ulcerative colitis and Crohn's disease are diseases with impaired epithelial barrier function. We aimed to investigate whether mutated prostasin and thus, reduced colonic epithelial sodium channel activity predisposes to develop an experimentally dextran sodium sulfate (DSS)-induced colitis. METHODS: Wildtype, heterozygous (fr/+), and homozygous (fr/fr) prostasin-mutant rats were treated 7 days with DSS followed by 7 days of recovery and analyzed with respect to histology, clinicopathological parameters, inflammatory marker mRNA transcript expression, and sodium transporter protein expression...
October 12, 2016: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/27543057/matriptase-and-prostasin-are-expressed-in-human-skin-in-an-inverse-trend-over-the-course-of-differentiation-and-are-targeted-to-different-regions-of-the-plasma-membrane
#9
Chih-Hsin Lai, Shun-Cheng Chang, Yen-Ju Chen, Yi-Jie J Wang, Ying-Jun J Lai, Hsiang-Hua D Chang, Eric B Berens, Michael D Johnson, Jehng-Kang Wang, Chen-Yong Lin
Matriptase and prostasin, acting as a tightly coupled proteolytic cascade, were reported to be required for epidermal barrier formation in mouse skin. Here we show that, in human skin, matriptase and prostasin are expressed with an inverse pattern over the course of differentiation. Matriptase was detected primarily in epidermal basal keratinocytes and the basaloid cells in the outer root sheath of hair follicles and the sebaceous gland, where prostasin was not detected. In contrast, prostasin was detected primarily in differentiated cells in the epidermal granular layer, the inner root sheath of hair follicles, and the sebaceous gland, where matriptase expression is negligible...
October 15, 2016: Biology Open
https://www.readbyqxmd.com/read/27459298/a-selective-irreversible-inhibitor-of-furin-does-not-prevent-pseudomonas-aeruginosa-exotoxin-a-induced-airway-epithelial-cytotoxicity
#10
Timothy E G Ferguson, James A Reihill, Brian Walker, Robert A Hamilton, S Lorraine Martin
Many bacterial and viral pathogens (or their toxins), including Pseudomonas aeruginosa exotoxin A, require processing by host pro-protein convertases such as furin to cause disease. We report the development of a novel irreversible inhibitor of furin (QUB-F1) consisting of a diphenyl phosphonate electrophilic warhead coupled with a substrate-like peptide (RVKR), that also includes a biotin tag, to facilitate activity-based profiling/visualisation. QUB-F1 displays greater selectivity for furin, in comparison to a widely used exemplar compound (furin I) which has a chloromethylketone warhead coupled to RVKR, when tested against the serine trypsin-like proteases (trypsin, prostasin and matriptase), factor Xa and the cysteine protease cathepsin B...
2016: PloS One
https://www.readbyqxmd.com/read/27385010/delineation-of-proteolytic-and-non-proteolytic-functions-of-the-membrane-anchored-serine-protease-prostasin
#11
Roman Szabo, Taliya Lantsman, Diane E Peters, Thomas H Bugge
The membrane-anchored serine proteases prostasin (PRSS8) and matriptase (ST14) initiate a cell surface proteolytic pathway essential for epithelial function. Mice expressing only catalytically inactive prostasin are viable, unlike prostasin null mice, indicating that at least some prostasin functions are non-proteolytic. Here we used knock-in mice expressing catalytically inactive prostasin (Prss8(Ki/Ki)) to show that the physiological and pathological functions of prostasin vary in their dependence on its catalytic activity...
August 1, 2016: Development
https://www.readbyqxmd.com/read/27081034/prss8-methylation-and-its-significance-in-esophageal-squamous-cell-carcinoma
#12
Yonghua Bao, Qian Wang, Yongchen Guo, Zhiguo Chen, Kai Li, Yiqiong Yang, Huijuan Zhang, Huali Dong, Kui Shen, Wancai Yang
Esophageal cancer is one of the most common cancers worldwide, and the incidence and mortality is increasing rapidly in recent years in China, but the underlying mechanisms are largely unclear. Herein we found that the expression of PRSS8, a serine protease prostasin, is significantly decreased in esophageal squamous cell carcinomas (ESCC) at mRNA and protein levels. The reduction of PRSS8 was well correlated with poor differentiation and shorter survival time. Interestingly, ESCC stromal expression of PRSS8 was significantly correlated with stromal lymphocyte infiltration and cancer progression...
May 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27050145/tumor-suppressor-prss8-targets-sphk1-s1p-stat3-akt-signaling-in-colorectal-cancer
#13
Yonghua Bao, Kai Li, Yongchen Guo, Qian Wang, Zexin Li, Yiqiong Yang, Zhiguo Chen, Jianguo Wang, Weixing Zhao, Huijuan Zhang, Jiwang Chen, Huali Dong, Kui Shen, Alan M Diamond, Wancai Yang
PRSS8 is a membrane-anchored serine protease prostasin and has been shown an association with carcinogenesis. Herein we found that PRSS8 expression was significantly reduced in colorectal adenomas and adenocarcinomas. The decreased PRSS8 was well correlated with clinical stages, poor differentiation and shorter survival time of colorectal cancer. Furthermore, increase of PRSS8 led to the inhibition of colorectal cancer cell proliferation, knockdown of PRSS8 accelerated cell proliferation in vitro, and overexpressing PRSS8 retarded cancer cell growth in nude mice...
May 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/27043831/matriptase-complexes-and-prostasin-complexes-with-hai-1-and-hai-2-in-human-milk-significant-proteolysis-in-lactation
#14
Chih-Hsin Lai, Ying-Jung J Lai, Feng-Pai Chou, Hsiang-Hua D Chang, Chun-Che Tseng, Michael D Johnson, Jehng-Kang Wang, Chen-Yong Lin
Significant proteolysis may occur during milk synthesis and secretion, as evidenced by the presence of protease-protease inhibitor complex containing the activated form of the type 2 transmembrane serine protease matriptase and the transmembrane Kunitz-type serine protease inhibitor HAI-1. In order to identify other proteolysis events that may occur during lactation, human milk was analyzed for species containing HAI-1 and HAI-2 which is closely related to HAI-1. In addition to the previously demonstrated matriptase-HAI-1 complex, HAI-1 was also detected in complex with prostasin, a glycosylphosphatidylinositol (GPI)-anchored serine protease...
2016: PloS One
https://www.readbyqxmd.com/read/27036110/the-serine-protease-prostasin-prss8-is-a-potential-biomarker-for-early-detection-of-ovarian-cancer
#15
Ayala Tamir, Anju Gangadharan, Sakshi Balwani, Takemi Tanaka, Ushma Patel, Ahmed Hassan, Stephanie Benke, Agnieszka Agas, Joseph D'Agostino, Dayoung Shin, Sunghoon Yoon, Andre Goy, Andrew Pecora, K Stephen Suh
BACKGROUND: Ovarian cancer (OVC) is the deadliest of all gynecologic cancers, primarily as a consequence of asymptomatic progression. The complex nature of OVC creates challenges for early detection, and there is a lack of specific and sensitive biomarkers suitable for screening and detecting early stage OVC. METHODS: Potential OVC biomarkers were identified by bioinformatic analysis. Candidates were further screened for differential expression in a library of OVC cell lines...
March 31, 2016: Journal of Ovarian Research
https://www.readbyqxmd.com/read/27014936/inhibition-of-protease-epithelial-sodium-channel-signaling-improves-mucociliary-function-in-cystic-fibrosis-airways
#16
James A Reihill, Brian Walker, Robert A Hamilton, Timothy E G Ferguson, J Stuart Elborn, M Jackson Stutts, Brian J Harvey, Vinciane Saint-Criq, Siobhan M Hendrick, S Lorraine Martin
RATIONALE: In cystic fibrosis (CF) a reduction in airway surface liquid (ASL) height compromises mucociliary clearance, favoring mucus plugging and chronic bacterial infection. Inhibitors of the epithelial sodium channel (ENaC) have therapeutic potential in CF airways to reduce hyperstimulated sodium and fluid absorption to levels that can restore airway hydration. OBJECTIVES: To determine whether a novel compound (QUB-TL1) designed to inhibit protease/ENaC signaling in CF airways restores ASL volume and mucociliary function...
September 15, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/26867056/prostasin-and-matriptase-st14-in-placenta-from-preeclamptic-and-healthy-pregnant-women
#17
Britta Frederiksen-Møller, Jan S Jørgensen, Mie R Hansen, Oliver Krigslund, Lotte K Vogel, Louise B Andersen, Boye L Jensen
OBJECTIVE: Preeclampsia is characterized by disturbed placentation, hypertension, proteinuria, and suppression of plasma renin, angiotensin II, and aldosterone. Regulated activity of tissue serine proteases, prostasin, and matriptase is necessary for normal placental development in mice. Prostasin activates the renal epithelial sodium channel. We hypothesized that preeclampsia is associated with low prostasin expression in placenta and spillover of prostasin into urine across the defect glomerular barrier...
February 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/26719335/distinct-developmental-functions-of-prostasin-cap1-prss8-zymogen-and-activated-prostasin
#18
Stine Friis, Daniel H Madsen, Thomas H Bugge
The membrane-anchored serine prostasin (CAP1/PRSS8) is essential for barrier acquisition of the interfollicular epidermis and for normal hair follicle development. Consequently, prostasin null mice die shortly after birth. Prostasin is found in two forms in the epidermis: a one-chain zymogen and a two-chain proteolytically active form, generated by matriptase-dependent activation site cleavage. Here we used gene editing to generate mice expressing only activation site cleavage-resistant (zymogen-locked) endogenous prostasin...
February 5, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/26682786/prostasin-proteases-and-preeclampsia
#19
EDITORIAL
Heather Y Small, Gemma E Currie, Christian Delles
No abstract text is available yet for this article.
February 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/26628676/urinary-proteolytic-activation-of-renal-epithelial-na-channels-in-chronic-heart-failure
#20
Hong Zheng, Xuefei Liu, Neeru M Sharma, Yulong Li, Rainer U Pliquett, Kaushik P Patel
One of the key mechanisms involved in renal Na(+) retention in chronic heart failure (CHF) is activation of epithelial Na(+) channels (ENaC) in collecting tubules. Proteolytic cleavage has an important role in activating ENaC. We hypothesized that enhanced levels of proteases in renal tubular fluid activate ENaC, resulting in renal Na(+) retention in rats with CHF. CHF was produced by left coronary artery ligation in rats. By immunoblotting, we found that several urinary serine proteases were significantly increased in CHF rats compared with sham rats (fold increases: furin 6...
January 2016: Hypertension
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