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Roman Szabo, Thomas H Bugge
Prostasin (CAP1/PRSS8) is a glycosylphosphatidylinositol (GPI)-anchored serine protease that is essential for epithelial development and overall survival in mice. Prostasin is regulated primarily by the transmembrane serine protease inhibitor, hepatocyte growth factor activator inhibitor (HAI)-2, and loss of HAI-2 function leads to early embryonic lethality in mice due to an unregulated prostasin activity. We have recently reported that critical in vivo functions of prostasin can be performed by proteolytically-inactive or zymogen-locked variants of the protease...
2018: PloS One
Ryo Ashida, Yukiyasu Okamura, Keiichi Ohshima, Yuko Kakuda, Katsuhiko Uesaka, Teiichi Sugiura, Takaaki Ito, Yusuke Yamamoto, Takashi Sugino, Kenichi Urakami, Masatoshi Kusuhara, Ken Yamaguchi
BACKGROUND/AIM: Project HOPE (High-tech Omics-based Patient Evaluation) began in 2014 using integrated gene expression profiling (GEP) of cancer tissues as well as diathesis of each patient who underwent operation at our Institution. The aim of this study was to identify novel genes displaying altered gene expression related to the survival and early recurrence after hepatectomy for hepatocellular carcinoma (HCC) using the results of integrated GEP analysis. MATERIALS AND METHODS: The present study included 92 patients...
November 2017: Cancer Genomics & Proteomics
Yonghua Bao, Qian Wang, Yongchen Guo, Zhiguo Chen, Kai Li, Yiqiong Yang, Huijuan Zhang, Huali Dong, Kui Shen, Wancai Yang
No abstract text is available yet for this article.
May 2, 2017: Oncotarget
Hu-Yin Yang, Da-Zhao Fang, Lian-Shu Ding, Xiao-Bo Hui, Dai Liu
Protease serine 8 (PRSS8), a serine peptidase, has a widespread expression in normal epidermal cells. Recently, many researchers demonstrated downregulation of PRSS8 in cancer tissues as well as its tumor suppressor role in cancer development. However, the biological functions of PRSS8 in glioma remain unclear. In the current study, we demonstrated a decreased expression of PRSS8 in glioma tissues and cell lines. PRSS8 upregulation inhibited glioma cell proliferation, migration, and invasion. In addition, xenograft experiments showed that PRSS8 overexpression suppressed glioma cell growth in vivo...
July 5, 2017: Oncology Research
Chaonan Ma, Wei Ma, Nannan Zhou, Na Chen, Li An, Yijie Zhang
Protease serine S1 family member 8 (PRSS8), a membrane-anchored serine protease, has been reported to be involved in the development of several human cancers. However, the role of PRSS8 in non-small cell lung cancer (NSCLC) pathogenesis remains unclear. The objective of this study was to investigate PRSS8 expression, biological function, and its related molecular mechanism in NSCLC. Our results showed that PRSS8 was expressed in a low amount in NSCLC cell lines. Ectopic expression of PRSS8 inhibited tumor growth in vitro and in vivo...
May 24, 2017: Oncology Research
Li Zhang, Guozhan Jia, Binya Shi, Guanqun Ge, Hongbin Duan, Yunsheng Yang
BACKGROUND: Protease serine 8 (PRSS8), a trypsin-like serine peptidase, has been shown to function as a tumour suppressor in various malignancies. The present study aimed to investigate the expression pattern, prognostic value and the biological role of PRSS8 in human hepatocellular carcinoma (HCC). METHODS: PRSS8 expression in 106 HCC surgical specimens was examined by Real-time polymerase chain reaction (PCR) and immunohistochemistry, and its clinical significance was analysed...
2016: Cellular Physiology and Biochemistry
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...
December 2016: Inflammatory Bowel Diseases
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
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
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
Kohei Uchimura, Kenichiro Kitamura
Serine proteases play pivotal roles in many biological processes including clotting, digestion, and immune system. A glycosylphosphatidylinositol-anchored serine protease prostasin(PRSS8) is ubiquitously expressed in many tissues such as kidney, prostate, skin, liver, lung, and colon. However, the physiological role for PRSS8 has not been fully understood. Recently, we have identified a novel role for PRSS8 in the regulation of glucose homeostasis via Toll-like receptor 4(TLR4)-mediated signaling in the liver and demonstrated new insight into the development of diabetes resulting from obesity-induced inflammation or metabolic endotoxemia...
March 2015: Nihon Rinsho. Japanese Journal of Clinical Medicine
Britta Frederiksen-Møller, Jan Stener Jørgensen, Lotte Katrine Vogel, Boye Lagerbon Jensen
OBJECTIVES: Serine proteases are enzymes involved in digestion, immune response, blood coagulation and reproduction. The serine protease prostasin (PRSS8, CAP1) and its regulatory associated proteins (Matriptase, Hepatocyt growth factor activator inhibitors (HAIs), and Nexin-1) are essential 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...
January 2015: Pregnancy Hypertension
Megha A Desai, Heather D Webb, Leander M Sinanan, J Neel Scarsdale, Ninad M Walavalkar, Gordon D Ginder, David C Williams
The MBD2-NuRD (Nucleosome Remodeling and Deacetylase) complex is an epigenetic reader of DNA methylation that regulates genes involved in normal development and neoplastic diseases. To delineate the architecture and functional interactions of the MBD2-NuRD complex, we previously solved the structures of MBD2 bound to methylated DNA and a coiled-coil interaction between MBD2 and p66α that recruits the CHD4 nucleosome remodeling protein to the complex. The work presented here identifies novel structural and functional features of a previously uncharacterized domain of MBD2 (MBD2IDR)...
March 31, 2015: Nucleic Acids Research
Giovanna Crisante, Laura Battista, Justyna Iwaszkiewicz, Valeria Nesca, Anne-Marie Mérillat, Chloé Sergi, Vincent Zoete, Simona Frateschi, Edith Hummler
Serine proteases, serine protease inhibitors, and protease-activated receptors (PARs) are responsible for several human skin disorders characterized by impaired epidermal permeability barrier function, desquamation, and inflammation. In this study, we addressed the consequences of a catalytically dead serine protease on epidermal homeostasis, the activation of PAR2 and the inhibition by the serine protease inhibitor nexin-1. The catalytically inactive serine protease CAP1/Prss8, when ectopically expressed in the mouse, retained the ability to induce skin disorders as well as its catalytically active counterpart (75%, n=81)...
November 2014: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Kurt W Kohn, Barry M Zeeberg, William C Reinhold, Yves Pommier
Using gene expression data to enhance our knowledge of control networks relevant to cancer biology and therapy is a challenging but urgent task. Based on the premise that genes that are expressed together in a variety of cell types are likely to functions together, we derived mutually correlated genes that function together in various processes in epithelial-like tumor cells. Expression-correlated genes were derived from data for the NCI-60 human tumor cell lines, as well as data from the Broad Institute's CCLE cell lines...
2014: PloS One
Diane E Peters, Roman Szabo, Stine Friis, Natalia A Shylo, Katiuchia Uzzun Sales, Kenn Holmbeck, Thomas H Bugge
The membrane-anchored serine protease prostasin (CAP1/PRSS8) is part of a cell surface proteolytic cascade that is essential for epithelial barrier formation and homeostasis. Here, we report the surprising finding that prostasin executes these functions independent of its own enzymatic activity. Prostasin null (Prss8(-/-)) mice lack barrier formation and display fatal postnatal dehydration. In sharp contrast, mice homozygous for a point mutation in the Prss8 gene, which causes the substitution of the active site serine within the catalytic histidine-aspartate-serine triad with alanine and renders prostasin catalytically inactive (Prss8(Cat-/Cat-) mice), develop barrier function and are healthy when followed for up to 20 weeks...
May 23, 2014: Journal of Biological Chemistry
Kohei Uchimura, Manabu Hayata, Teruhiko Mizumoto, Yoshikazu Miyasato, Yutaka Kakizoe, Jun Morinaga, Tomoaki Onoue, Rika Yamazoe, Miki Ueda, Masataka Adachi, Taku Miyoshi, Naoki Shiraishi, Wataru Ogawa, Kazuki Fukuda, Tatsuya Kondo, Takeshi Matsumura, Eiichi Araki, Kimio Tomita, Kenichiro Kitamura
The effects of high-fat diet (HFD) and postprandial endotoxemia on the development of type 2 diabetes are not fully understood. Here we show that the serine protease prostasin (PRSS8) regulates hepatic insulin sensitivity by modulating Toll-like receptor 4 (TLR4)-mediated signalling. HFD triggers the suppression of PRSS8 expression by inducing endoplasmic reticulum (ER) stress and increases the TLR4 level in the liver. PRSS8 releases the ectodomain of TLR4 by cleaving it, which results in a reduction in the full-length form and reduces the activation of TLR4...
2014: Nature Communications
Sumedha Malsure, Qing Wang, Roch-Philippe Charles, Chloe Sergi, Romain Perrier, Birgitte Mønster Christensen, Marc Maillard, Bernard C Rossier, Edith Hummler
Aldosterone promotes electrogenic sodium reabsorption through the amiloride-sensitive epithelial sodium channel (ENaC). Here, we investigated the importance of ENaC and its positive regulator channel-activating protease 1 (CAP1/Prss8) in colon. Mice lacking the αENaC subunit in colonic superficial cells (Scnn1a(KO)) were viable, without fetal or perinatal lethality. Control mice fed a regular or low-salt diet had a significantly higher amiloride-sensitive rectal potential difference (∆PDamil) than control mice fed a high-salt diet...
July 2014: Journal of the American Society of Nephrology: JASN
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