324,348 research outputs found
RECK as a Potential Crucial Molecule for the Targeted Treatment of Sepsis
No full textYuting Qin,1,* Shuanglin Liao,1,* Jianbo Sun,2 Huiyun Ye,1 Jiafu Li,1 Jiahui Pan,1 Junbing He,3 Zhengyuan Xia,4,5 Yiming Shao1,6 1Dongguan Key Laboratory of Sepsis Translational Medicine, The Intensive Care Unit, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, Guangdong, People’s Republic of China; 2Dongguan Key Laboratory of Chronic Inflammatory Diseases, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, Guangdong, People’s Republic of China; 3The Key Laboratory of Organ Dysfunction and Protection Translational Medicine, Jieyang Medical Research Center, Jieyang People’s Hospital, Jieyang, Guangdong, People’s Republic of China; 4Department of Anesthesiology and Perioperative Medicine, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, People’s Republic of China; 5State Key Laboratory of Pharmaceutical Biotechnology, Department of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, People’s Republic of China; 6The Key Laboratory of Sepsis Translational Medicine, Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yiming Shao, Dongguan Key Laboratory of Sepsis Translational Medicine, the Intensive Care Unit,The First Dongguan Affiliated Hospital, Guangdong Medical University, Jiaoping Road 42, Tangxia Town, Dongguan, Guangdong Province, 523710, People’s Republic of China, Tel +86 18826690188, Email [email protected] Zhengyuan Xia, Department of Anesthesiology and Perioperative Medicine, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, People’s Republic of China, Tel +852-68798794, Email [email protected]: Reversion inducing cysteine rich protein with kazal motifs (RECK), a Kazal motif-containing protein, regulates pro-inflammatory cytokines production, migration of inflammatory cells, vascular endothelial growth factor (VEGF) and Wnt pathways and plays critical roles in septic inflammatory storms and vascular endothelial dysfunction. Recently, RECK has been defined as the negative regulator of adisintegrin and metalloproteinases (ADAMs) and matrix metalloproteinases (MMPs), which are both membrane “molecular scissors” and aggravate the poor prognosis of sepsis. To better understand the roles of RECK and the related mechanisms, we make here a systematic and in-depth review of RECK. We first summarize the findings on structural characteristics of RECK protein and the regulation at the transcription, post-transcription, or protein level of RECK. Then, we discuss the roles of RECK in inflammation, infection, and vascular injury by focusing on the RECK function on ADAMs and MMPs, as well as the pathways of VEGF, WNT, angiopoietin, and notch signaling. In conclusion, RECK participation as a guardian in the development of sepsis provides insight into the strategies of precisely intervening in RECK dysregulationfor the treatment of sepsis.Keywords: RECK, sepsis, vascular endothelial function regulation, inflammatio
Wirklich wahre Wirklichkeit VL 01
No full textVL 1: 21. 10. 2013
Anhand von Buñuel und Pasolini
In der ersten Vorlesung bietet Hans Ulrich Reck eine kurze Einführung und
Erläuterungen dar der Inhalte, Formen, Arbeitsweisen und Anforderungen. Behandelte
Themen: Luis Buñuel, Surrealismus, Buñuel/ Dali, 'Ein andalusischer Hund'; Exkurs zu
Pier Paolo Pasolini ('Sopraluoghi' und 'Appunti'; Auszüge aus der 'afrikanischen Orestie'
und zu Palestina).
Texte:
– Stichworte 'Film und Traum' und 'Surrealismus' (versch. Eintragungen in:) Hans Ulrich
Reck, Traum. Enzyklopädie, München 2010, S. 421-432 und 623-640
– Hans Ulrich Reck, 'Dunkle Erkundungen eines verstummenden Echos' Natur und
surrealistischer Film, in: Hans Ulrich Reck, Spiel Form Künste. Zu einer Kunstgeschichte des
Improvisierens, Hamburg 2010,. S. 115-153
– Karin Orchard/ Jörg Zimmermann (Hrsg.), Die Er!ndung der Natur. Max Ernst, Paul Klee,
Wols und das surreale Universum, Ausstellungskat. Sprengel Museum Hannover, Freiburg,
1994
– Hans Ulrich Reck, Pier Paolo Pasolini, München: Fink (Reihe 'directed by') 2010, bes. S.
71-106 (Kapitel 'Arbeitsweise: Film und Kino als kinematographische Untersuchungen zu
einer Semiotik des Realen')
– Film-Traum-Bild bei Pasolini, in: Hans Ulrich Reck, Traum. Enzyklopädie, München
2010, S. 432-43
Evaluation of Reck tumor supressor gene`s role in neuronal differentiation.
No full textO gene supressor de tumor Reck (REversion-inducing Cysteine-rich protein with Kazal motifs) codifica uma glicoproteína multifuncional que inibe a atividade de diversas metaloproteinases de matriz (MMPs), como também modula a atividade de Notch e vias de Wnt canônico. Células neuroprogenitoras com Reck deficiente sofrem uma diferenciação precoce, entretanto, a modulação da expressão de Reck durante a progressão da diferenciação neuronal ainda precisa ser caracterizada. No presente estudo, nós verificamos a assinatura da expressão de Reck e caracterizamos a atividade do promotor de Reck murino durante o processo de diferenciação neural. Foi possível verificar um aumento na atividade e níveis de expressão do promotor de Reck em três modelos de diferenciação celular: PC12 feocromocitoma, P19 teratocarcinoma derivado de embrião e USP-4 célula tronco embrionária de murinos, que foram submetidas a indução da neurodiferenciação. Além disso, a superexpressão de Reck antes do início da diferenciação celular leva a uma diminuição na eficiência do processo de neurodiferenciação. Levando em conta os dois dados obtidos, eles sugerem que em oposição ao aumento gradual de Reck durante a diferenciação neuronal, a superexpressão nos estágios mais precoces de diferenciação dificulta as células progenitoras a se comprometerem com o destino para células neuronais. Nossos dados reforçam o potencial do uso da modulação da expressão de Reck para otimização dos protocolos de diferenciação in vitro.Reck (REversion-inducing Cysteine-rich protein with Kazal motifs) tumor suppressor gene encodes a multifunctional glycoprotein that inhibits the activity of several matrix metalloproteinases (MMPs) and is also able to modulate the Notch and canonical Wnt pathways. Reck-deficient neuroprogenitor cells undergo precocious differentiation; however, modulation of Reck expression during progression of neuronal differentiation process is yet to be characterized. In the present study, we assessed the Reck expression signature and characterized the mouse Reck promoter activity during the in vitro neural differentiation process. We found increased Reck promoter activity and expression levels in three different cellular models, namely: PC12 pheochromocitoma, P19 embryo-derived teratocarcinoma and USP-4 murine embryonic stem cells, upon subjection to neurodifferentiation induction. Moreover, Reck overexpression prior to the beginning of the differentiation protocol leads to diminished efficiency of the neurodifferentiation process. Taken together, our findings suggest that in opposition to the gradual increase of Reck expression during the neuronal differentiation process, its overexpression at early stages of the process hinders the progenitor cells commitment to a neuronal fate. Our data reinforces the potential use of Reck expression modulation to optimize in vitro neurodifferentiation protocols
Экспрессия ингибитора мембраносвязанных матриксных металлопротеиназ RECK в линиях в линиях опухолевых клеток мыши
No full textAim: It has been demonstrated that the endogenous matrix metalloproteinases (MMPs) inhibitor reversion inducing cysteine rich protein with Kazal motifs (RECK) is a reliable prognostic marker for detecting several types of tumors. However, the RECK expressions in most of the normal and neoplastic tissues were extremely low, and to measure its expression is quite complicated. The purpose of the present study is to establish an easy method to quantify murine RECK mRNA expression for use in future experimental studies. Subsequently, in order to verify the reliability of the established quantification technique, we examined the change in RECK expression and gelatinase secretion in tumor cells when stimulated by the extracellular matrix. Methods: Several murine tumor cells were used in the present study. The real-time polymerase chain reaction (PCR) method and measurement conditions for murine RECK mRNA were studied using these tumor cells. Gelatinase activities were also examined by gelatin zymography. Results: Murine RECK mRNA expression was accurately quantified using real-time PCR. Among the tumor cells used in the study, osteosarcoma cells showed significantly higher RECK mRNA expression than the others. The RECK expression in the osteosarcoma cells was down-regulated by contact with matrigel-coated culture flasks due to increased secretion of gelatinases. Conclusion: The real-time PCR method employed in our study is useful to quantify RECK expression.Показано, что эндогенный ингибитор матриксных протеиназ (MMП) RECK может служить надежным прогностическим
маркером для некоторых типов опухолей, однако его экспрессия в большинстве нормальных и неопластических тканей
крайне низкая, поэтому возникают сложности, связанные с детекцией таковой. Цель работы — разработка количественного
метода определения экспрессии мРНК для использования в экспериментальных исследованиях. Для дальнейшего
подтверждения надежности разработанного метода исследованы изменения экспрессии RECK и секреции желатиназ в
опухолевых клетках при стимуляции внеклеточным матриксом. Методы: в работе использовали несколько линий опухолевых
клеток мыши, в которых экспрессию мРНК RECK анализировали методом ПЦР в режиме реального времени,
активность желатиназ — методом зимографии. Результаты: экспрессию мРНК RECK количественно оценили методом
ПЦР в режиме реального времени, причем среди исследованных клеточных линий наиболее высокий уровень экспрессии
RECK выявили в клетках остеосаркомы. Экспрессия RECK в клетках остеосаркомы подавлялась при контакте с культуральным
пластиком, обработанным матригелем, вследствие повышения секреции желатиназ. Выводы: для количественной
оценки экспрессии мРНК RECK может быть использован метод ПЦР в режиме реального времени
Analysis of the inhibiting activity of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) on matrix metalloproteinases
No full text© The Author(s) 2020.Matrix metalloproteinases (MMPs) occur in 23 human paralogues with key functions in physiology, and their activity is controlled by protein inhibitors. Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), which is essential for embryogenesis and tumour suppression, has been reported to inhibit MMPs. Here, we developed eukaryotic and bacterial expression systems for different RECK variants and analysed their inhibitory capacity against representative MMPs in vitro. We could not detect any significant inhibition. Instead, we found that partially purified RECK from the conditioned medium of transfected Expi293F cells but not that of ExpiCHO-S or Drosophila Schneider cells contained a contaminant with proteolytic activity. The contaminant was removed through treatment with a small-molecule serine peptidase inhibitor and additional chromatographic purification. A tantamount contaminant was further detected in an equivalent expression system of the N-terminal fragment of the proteoglycan testican 3, but not in those of two other proteins. These results indicate that previous reports of inhibitory activity of recombinant RECK on MMPs, which were performed with partially purified samples, were probably masked by a coeluting contaminant present in the supernatant of HEK293-derived cells. Thus, RECK is probably not a direct inhibitor of MMP catalytic activity but may still regulate MMPs through other mechanisms.This study was supported in part by grants from Spanish and Catalan public and private bodies (grant/ fellowship references BFU2015–64487R, MDM-2014–0435, BES-2015–074583, BES-2016–076877, 2017SGR3 and Fundació “La Marató de TV3” 201815)
Экспрессия ингибитора мембраносвязанных матриксных металлопротеиназ RECK в линиях в линиях опухолевых клеток мыши
No full textAim: It has been demonstrated that the endogenous matrix metalloproteinases (MMPs) inhibitor reversion inducing cysteine rich protein with Kazal motifs (RECK) is a reliable prognostic marker for detecting several types of tumors. However, the RECK expressions in most of the normal and neoplastic tissues were extremely low, and to measure its expression is quite complicated. The purpose of the present study is to establish an easy method to quantify murine RECK mRNA expression for use in future experimental studies. Subsequently, in order to verify the reliability of the established quantification technique, we examined the change in RECK expression and gelatinase secretion in tumor cells when stimulated by the extracellular matrix. Methods: Several murine tumor cells were used in the present study. The real-time polymerase chain reaction (PCR) method and measurement conditions for murine RECK mRNA were studied using these tumor cells. Gelatinase activities were also examined by gelatin zymography. Results: Murine RECK mRNA expression was accurately quantified using real-time PCR. Among the tumor cells used in the study, osteosarcoma cells showed significantly higher RECK mRNA expression than the others. The RECK expression in the osteosarcoma cells was down-regulated by contact with matrigel-coated culture flasks due to increased secretion of gelatinases. Conclusion: The real-time PCR method employed in our study is useful to quantify RECK expression.Показано, что эндогенный ингибитор матриксных протеиназ (MMП) RECK может служить надежным прогностическим
маркером для некоторых типов опухолей, однако его экспрессия в большинстве нормальных и неопластических тканей
крайне низкая, поэтому возникают сложности, связанные с детекцией таковой. Цель работы — разработка количественного
метода определения экспрессии мРНК для использования в экспериментальных исследованиях. Для дальнейшего
подтверждения надежности разработанного метода исследованы изменения экспрессии RECK и секреции желатиназ в
опухолевых клетках при стимуляции внеклеточным матриксом. Методы: в работе использовали несколько линий опухолевых
клеток мыши, в которых экспрессию мРНК RECK анализировали методом ПЦР в режиме реального времени,
активность желатиназ — методом зимографии. Результаты: экспрессию мРНК RECK количественно оценили методом
ПЦР в режиме реального времени, причем среди исследованных клеточных линий наиболее высокий уровень экспрессии
RECK выявили в клетках остеосаркомы. Экспрессия RECK в клетках остеосаркомы подавлялась при контакте с культуральным
пластиком, обработанным матригелем, вследствие повышения секреции желатиназ. Выводы: для количественной
оценки экспрессии мРНК RECK может быть использован метод ПЦР в режиме реального времени
Decreased RECK and Increased EMMPRIN Expression in Urothelial Carcinoma of the Bladder Are Associated with Tumor Aggressiveness
No full text<i>Objective:</i> Urothelial bladder carcinomas show a divergent biological behavior, which significantly complicates risk stratification and clinical management. The MMP repressor RECK and the MMP activator EMMPRIN regulate the invasive potential by metalloproteinase-induced stromal degradation. Data on RECK in urothelial bladder cancer are lacking and information on EMMPRIN is sparse. This study aims to investigate the expression of RECK and EMMPRIN in urothelial carcinoma of the bladder and to correlate these findings with clinicopathological parameters. <i>Methods:</i> Our study included 127 specimens of urothelial carcinomas derived from 103 patients who underwent either TUR-B or cystectomy. Immunohistochemical expression analysis was performed for RECK, EMMPRIN, MMP-2, MMP-9 and MMP-14. Expression levels were graded for staining intensity and correlated with pT stage and WHO tumor grade. <i>Results:</i> Invasive (≧pT1) as well as WHO high-grade urothelial carcinomas showed a statistically significant and stepwise downregulation of RECK (p < 0.001) and concomitant upregulation of EMMPRIN (p < 0.001) compared to non-invasive and WHO low-grade tumors. No correlation was observed for the MMPs investigated. <i>Conclusion:</i> Decreased RECK and increased EMMPRIN expression are associated with increasing stage and grade. Both proteins may serve as molecular marker for the distinction between potentially invasive (≧pT1) and non-invasive tumors (≤pTa).</jats:p
Suppression of Non-Small Cell Lung Cancer Growth and Metastasis by a Novel Small Molecular Activator of RECK
No full textBackground/Aims: Reversion-inducing cysteine-rich protein with kazal motifs (RECK) is a novel tumor suppressor gene that is critical for regulating tumor cell invasion and metastasis. The expression of RECK is dramatically down-regulated in human cancers. Harmine, a tricyclic compound from Peganum harmala, has been shown to have potential anti-cancer activity. Methods: Cell proliferation assay (CCK-8 cell viability assay), cell cycle analysis (detection by flow cytometry), apoptosis staining assay (TUNEL staining), cell migration assay and invasion assay (transwell assay) were carried out to investigate the Harmine’s efficacy on non-small cell lung cancer (NSCLC) cells in vitro. A549-luciferase cell orthotropic transplantation xenograft mouse model was used to determine the effect of Harmine treatment on NSCLC in vivo. Western blotting analysis of cell growth and metastasis related signal pathways was conducted to investigate the molecular mechanism of Harmine’s inhibitory effect on NSCLC. Results: Harmine treatment effectively inhibited cell proliferation and induced the G1/S cell cycle arrest of NSCLC cells. Further study proved that Harmine treatment led to apoptosis induction. Furthermore, treatment with NSCLC cells with Hamine resulted in decreased cell migration and cell invasion in vitro. More importantly, Harmine treatment significantly suppressed the NSCLC tumor growth and metastasis in mouse xenograft model in vivo. Mechanistically, in Harmine-treated NSCLC cells, RECK expression and its downstream signaling cascade were dramatically activated. As a consequence, the expression level of MMP-9 and E-cadherin were significantly decreased. Conclusion: These findings identify Harmine as a promising activator of RECK signaling for metastatic NSCLC treatment.</jats:p
The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis.
No full textMatrix metalloproteinases (MMPs) are essential for proper extracellular matrix remodeling. We previously found that a membrane-anchored glycoprotein, RECK, negatively regulates MMP-9 and inhibits tumor invasion and metastasis. Here we show that RECK regulates two other MMPs, MMP-2 and MT1-MMP, known to be involved in cancer progression, that mice lacking a functional RECK gene die around E10.5 with defects in collagen fibrils, the basal lamina, and vascular development, and that this phenotype is partially suppressed by MMP-2 null mutation. Also, vascular sprouting is dramatically suppressed in tumors derived from RECK-expressing fibrosarcoma cells grown in nude mice. These results support a role for RECK in the regulation of MMP-2 in vivo and implicate RECK downregulation in tumor angiogenesis
Ellagic acid upregulated the RECK expression.
No full text<p>The effect of EA treatment for 24 hours on the expression of RECK in HUVECs was analyzed at the A. mRNA and B. protein levels as measured by RT-PCR and Western blot analysis.</p
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