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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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Heather Y Small, Gemma E Currie, Christian Delles
No abstract text is available yet for this article.
February 2016: Journal of Hypertension
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
Wei Xu, Seok Jong Hong, Aimei Zhong, Ping Xie, Shengxian Jia, Zhong Xie, Michael Zeitchek, Solmaz Niknam-Bienia, Jingling Zhao, D Marshall Porterfield, D James Surmeier, Kai P Leung, Robert D Galiano, Thomas A Mustoe
The mechanisms by which the epidermis responds to disturbances in barrier function and restores homeostasis are unknown. With a perturbation of the epidermal barrier, water is lost, resulting in an increase in extracellular sodium concentration. We demonstrate that the sodium channel Nax functions as a sodium sensor. With increased extracellular sodium, Nax up-regulates prostasin, which results in activation of the sodium channel ENaC, resulting in increased sodium flux and increased downstream mRNA synthesis of inflammatory mediators...
November 4, 2015: Science Translational Medicine
Weiqi Kong, Yanyan Zhang, Yunhui Gong, Li Dai, Rong Zhou
OBJECTIVE: To assess the association of prostasin gene rs12597511 polymorphism with clinical features and pregnancy outcomes among patients with severe preeclampsia. METHODS: Clinical manifestations, pregnancy outcomes and the genotypes of 179 patients with severe preeclampsia [early-onset group (≤34 gestational weeks): 79 cases; Late-onset group (>34 gestational weeks): 100 cases] and 222 normal-term pregnant women (control group) were collected. RESULTS: In the early-onset group, the patients with TC or CC genotype at rs12597511 had higher incidences of total complications, liver dysfunction, neonatal asphyxia, neonatal intracranial hemorrhage and perinatal mortality compared with those with TT genotype (P>0...
August 2015: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
B L Jensen, B Frederiksen-Moller, J S Jorgensen, L Vogel, O Krigslund, L B Andersen
OBJECTIVE: The serine protease prostasin (PRSS8, CAP1) and its activator matriptase and inhibitor nexin-1 are necessary for normal placental development in mice. Prostasin is regulated by aldosterone in the kidney and may activate the epithelial sodium channel (ENaC). Preeclampsia is characterized by disturbed placentation, suppression of aldosterone and avid renal sodium retention with hypertension. It was hypothesized that preeclampsia is associated with low prostasin expression in placenta and spillover of prostasin into urine across the defect glomeular barrier...
June 2015: Journal of Hypertension
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