LIVIVO - Search results -

Search results

Result 1 - 10 of total 17

Search options

Article ; Online: [Not Available].

Lakner, Ashley M / Steuerwald, Nury M / Schrum, Laura W

2013 Volume 57, Issue 3, Page(s) 1286–1287

MeSH term(s)	Animals ; Hepatic Stellate Cells/metabolism ; Humans ; Liver Cirrhosis/pathology ; Male ; MicroRNAs/genetics ; Transforming Growth Factor beta/metabolism
Chemical Substances	MicroRNAs ; Transforming Growth Factor beta
Language	English
Publishing date	2013-03
Publishing country	United States
Document type	Comment ; Letter
ZDB-ID	604603-4
ISSN	1527-3350 ; 0270-9139
ISSN (online)	1527-3350
ISSN	0270-9139
DOI	10.1002/hep.25997
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1660: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾

Article ; Online: microRNAs: fad or future of liver disease.

Lakner, Ashley M / Bonkovsky, Herbert L / Schrum, Laura W

World journal of gastroenterology

2011 Volume 17, Issue 20, Page(s) 2536–2542

Abstract: microRNAs (miRs) are small non-coding RNAs that regulate both mRNA and protein expression of target genes, which results in alterations in mRNA stability or translation inhibition. miRs influence at least one third of all human transcripts and are known ... ...

Abstract	microRNAs (miRs) are small non-coding RNAs that regulate both mRNA and protein expression of target genes, which results in alterations in mRNA stability or translation inhibition. miRs influence at least one third of all human transcripts and are known regulators of various important cellular growth and differentiation factors. miRs have recently emerged as key regulatory molecules in chronic liver disease. This review details recent contributions to the field of miRs that influence liver development and the broad spectrum of disease, from non-alcoholic fatty liver disease to fibrosis/cirrhosis, with particular emphasis on hepatic stellate cells and potential use of miRs as therapeutic tools.
MeSH term(s)	Animals ; Fatty Liver/physiopathology ; Humans ; Liver Cirrhosis/physiopathology ; Liver Diseases/drug therapy ; Liver Diseases/physiopathology ; Liver Regeneration/physiology ; MicroRNAs/physiology ; MicroRNAs/therapeutic use ; Non-alcoholic Fatty Liver Disease
Chemical Substances	MicroRNAs
Language	English
Publishing date	2011-04-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2185929-2
ISSN	2219-2840 ; 1007-9327
ISSN (online)	2219-2840
ISSN	1007-9327
DOI	10.3748/wjg.v17.i20.2536
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 6039: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Nonmuscle myosin II regulates migration but not contraction in rat hepatic stellate cells.

Moore, Cathy C / Lakner, Ashley M / Yengo, Christopher M / Schrum, Laura W

World journal of hepatology

2011 Volume 3, Issue 7, Page(s) 184–197

Abstract: Aim: To identify and characterize the function of nonmuscle myosin II (NMM II) isoforms in primary rat hepatic stellate cells (HSCs).: Methods: Primary HSCs were isolated from male Sprague-Dawley rats by pronase/collagenase digestion. Total RNA and ... ...

Abstract	Aim: To identify and characterize the function of nonmuscle myosin II (NMM II) isoforms in primary rat hepatic stellate cells (HSCs). Methods: Primary HSCs were isolated from male Sprague-Dawley rats by pronase/collagenase digestion. Total RNA and protein were harvested from quiescent and culture-activated HSCs. NMM II isoform (II-A, II-B and II-C) gene and protein expression were measured by RealTime polymerase chain reaction and Western blot analyses respectively. NMM II protein localization was visualized in vitro using immunocytochemical analysis. For in vivo assessment, liver tissue was harvested from bile duct-ligated (BDL) rats and NMM IIisoform expression determined by immunohistochemistry. Using a selective myosin II inhibitor and siRNA-mediated knockdown of each isoform, NMM II functionality in primary rat HSCs was determined by contraction and migration assays. Results: NMM II-A and II-B mRNA expression was increased in culture-activated HSCs (Day 14) with significant increases seen in all pair-wise comparisons (II-A: 12.67 ± 0.99 (quiescent) vs 17.36 ± 0.78 (Day 14), P < 0.05; II-B: 4.94 ± 0.62 (quiescent) vs 13.90 ±0.85 (Day 14), P < 0.001). Protein expression exhibited similar expression patterns (II-A: 1.87 ± 2.50 (quiescent) vs 58.64 ± 8.76 (Day 14), P < 0.05; II-B: 1.17 ± 1.93 (quiescent) vs 103.71 ± 21.73 (Day 14), P < 0.05). No significant differences were observed in NMM II-C mRNA and protein expression between quiescent and activated HSCs. In culture-activated HSCs, NMM II-A and II-B merged with F-actin at the cellular periphery and throughout cytoplasm respectively. In vitro studies showed increased expression of NMM II-B in HSCs activated by BDL compared to sham-operated animals. There were no apparent increases of NMM II-A and II-C protein expression in HSCs during hepatic BDL injury. To determine the contribution of NMM II-A and II-B to migration and contraction, NMM II-A and II-B expression were downregulated with siRNA. NMM II-A and/or II-B siRNA inhibited HSC migration by approximately 25% compared to scramble siRNA-treated cells. Conversely, siRNA-mediated NMM II-A and II-B inhibition had no significant effect on HSC contraction; however, contraction was inhibited with the myosin II inhibitor, blebbistatin (38.7% ± 1.9%). Conclusion: Increased expression of NMM II-A and II-B regulates HSC migration, while other myosin IIclasses likely modulate contraction, contributing to development and severity of liver fibrosis.
Language	English
Publishing date	2011-08-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2573703-X
ISSN	1948-5182 ; 1948-5182
ISSN (online)	1948-5182
ISSN	1948-5182
DOI	10.4254/wjh.v3.i7.184
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Daily genetic profiling indicates JAK/STAT signaling promotes early hepatic stellate cell transdifferentiation

Ashley M Lakner, Cathy C Moore, Alyssa A Gulledge, Laura W Schrum

World Journal of Gastroenterology, Vol 16, Iss 40, Pp 5047-

2010 Volume 5056

Abstract: AIM: To identify signaling pathways and genes that initiate and commit hepatic stellate cells (HSCs) to transdifferentiation.METHODS: Primary HSCs were isolated from male Sprague-Dawley rats and cultured on plastic for 0-10 d. Gene expression was ... ...

Abstract	AIM: To identify signaling pathways and genes that initiate and commit hepatic stellate cells (HSCs) to transdifferentiation.METHODS: Primary HSCs were isolated from male Sprague-Dawley rats and cultured on plastic for 0-10 d. Gene expression was assessed daily (quiescent to day 10 culture-activation) by real time polymerase chain reaction and data clustered using AMADA software. The significance of JAK/STAT signaling to HSC transdifferentiation was determined by treating cells with a JAK2 inhibitor.RESULTS: Genetic cluster analyses, based on expression of these 21 genes, showed similar expression profiles on days 1-3, days 5 and 6, and days 7-10, while freshly isolated cells (day Q) and day 4 cells were genotypically distinct from any of the other days. Additionally, gene expression clustering revealed strong upregulation of interleukin-6, JAK2 and STAT3 mRNA in the early stages of activation. Inhibition of the JAK/STAT signaling pathway impeded the morphological transdifferentiation of HSCs which correlated with decreased mRNA expression of several profibrotic genes including collagens, α-SMA, PDGFR and TGFβR.CONCLUSION: These data demonstrate unique clustered genetic profiles during the daily progression of HSC transdifferentiation and that JAK/STAT signaling may be critical in the early stages of transdifferentiation.
Keywords	Cluster analysis ; Fibrosis ; Genetic profile ; Hepatic stellate cell ; Interleukin-6 ; Diseases of the digestive system. Gastroenterology ; RC799-869 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Gastroenterology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	572
Language	English
Publishing date	2010-10-01T00:00:00Z
Publisher	Baishideng Publishing Group Co. Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Daily genetic profiling indicates JAK/STAT signaling promotes early hepatic stellate cell transdifferentiation.

Lakner, Ashley M / Moore, Cathy C / Gulledge, Alyssa A / Schrum, Laura W

World journal of gastroenterology

2010 Volume 16, Issue 40, Page(s) 5047–5056

Abstract: Aim: To identify signaling pathways and genes that initiate and commit hepatic stellate cells (HSCs) to transdifferentiation.: Methods: Primary HSCs were isolated from male Sprague-Dawley rats and cultured on plastic for 0-10 d. Gene expression was ... ...

Abstract	Aim: To identify signaling pathways and genes that initiate and commit hepatic stellate cells (HSCs) to transdifferentiation. Methods: Primary HSCs were isolated from male Sprague-Dawley rats and cultured on plastic for 0-10 d. Gene expression was assessed daily (quiescent to day 10 culture-activation) by real time polymerase chain reaction and data clustered using AMADA software. The significance of JAK/STAT signaling to HSC transdifferentiation was determined by treating cells with a JAK2 inhibitor. Results: Genetic cluster analyses, based on expression of these 21 genes, showed similar expression profiles on days 1-3, days 5 and 6, and days 7-10, while freshly isolated cells (day Q) and day 4 cells were genotypically distinct from any of the other days. Additionally, gene expression clustering revealed strong upregulation of interleukin-6, JAK2 and STAT3 mRNA in the early stages of activation. Inhibition of the JAK/STAT signaling pathway impeded the morphological transdifferentiation of HSCs which correlated with decreased mRNA expression of several profibrotic genes including collagens, α-SMA, PDGFR and TGFβR. Conclusion: These data demonstrate unique clustered genetic profiles during the daily progression of HSC transdifferentiation and that JAK/STAT signaling may be critical in the early stages of transdifferentiation.
MeSH term(s)	Actins/genetics ; Actins/metabolism ; Animals ; Cell Transdifferentiation/physiology ; Cells, Cultured ; Collagen/genetics ; Collagen/metabolism ; Gene Expression Profiling ; Hepatic Stellate Cells/cytology ; Hepatic Stellate Cells/metabolism ; Interleukin-6/genetics ; Interleukin-6/metabolism ; Janus Kinase 2/genetics ; Janus Kinase 2/metabolism ; Male ; Models, Animal ; Rats ; Rats, Sprague-Dawley ; Receptors, Platelet-Derived Growth Factor/genetics ; Receptors, Platelet-Derived Growth Factor/metabolism ; Receptors, Transforming Growth Factor beta/genetics ; Receptors, Transforming Growth Factor beta/metabolism ; STAT3 Transcription Factor/genetics ; STAT3 Transcription Factor/metabolism ; Signal Transduction/physiology
Chemical Substances	Actins ; Interleukin-6 ; Receptors, Transforming Growth Factor beta ; STAT3 Transcription Factor ; Stat3 protein, rat ; smooth muscle actin, rat ; Collagen (9007-34-5) ; Receptors, Platelet-Derived Growth Factor (EC 2.7.10.1) ; Jak2 protein, rat (EC 2.7.10.2) ; Janus Kinase 2 (EC 2.7.10.2)
Language	English
Publishing date	2010-10-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2185929-2
ISSN	2219-2840 ; 1007-9327
ISSN (online)	2219-2840
ISSN	1007-9327
DOI	10.3748/wjg.v16.i40.5047
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 6039: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: microRNAs

Ashley M Lakner / Herbert L Bonkovsky / Laura W Schrum

World Journal of Gastroenterology, Vol 17, Iss 20, Pp 2536-

Fad or future of liver disease

2011 Volume 2542

Abstract	microRNAs (miRs) are small non-coding RNAs that regulate both mRNA and protein expression of target genes, which results in alterations in mRNA stability or translation inhibition. miRs influence at least one third of all human transcripts and are known regulators of various important cellular growth and differentiation factors. miRs have recently emerged as key regulatory molecules in chronic liver disease. This review details recent contributions to the field of miRs that influence liver development and the broad spectrum of disease, from non-alcoholic fatty liver disease to fibrosis/cirrhosis, with particular emphasis on hepatic stellate cells and potential use of miRs as therapeutic tools.
Keywords	Liver ; Fibrosis ; microRNA ; mRNA ; Hepatic stellate cells ; Diseases of the digestive system. Gastroenterology ; RC799-869 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Gastroenterology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	610
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	Baishideng Publishing Group Co., Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Altered aquaporin expression and role in apoptosis during hepatic stellate cell activation.

Lakner, Ashley M / Walling, Tracy L / McKillop, Iain H / Schrum, Laura W

Liver international : official journal of the International Association for the Study of the Liver

2010 Volume 31, Issue 1, Page(s) 42–51

Abstract: Background: Hepatic stellate cells (HSCs) are effector cells of hepatic fibrosis contributing to excessive collagen deposition and scar matrix formation. Sustained HSC activation leads to hepatic cirrhosis, a leading cause of liver-related death. ... ...

Abstract	Background: Hepatic stellate cells (HSCs) are effector cells of hepatic fibrosis contributing to excessive collagen deposition and scar matrix formation. Sustained HSC activation leads to hepatic cirrhosis, a leading cause of liver-related death. Reversal of hepatic fibrosis has been attributed to the induction of HSC apoptosis. Aquaporins (AQPs) are critical proteinacious channels that mediate cellular water loss during the initiation and progression of apoptosis. Aims: This study examined AQP expression in quiescent and activated HSCs and determined the responsiveness to AQP-dependent apoptosis. Methods: Aquaporin gene and protein expressions in quiescent and activated HSCs were determined by reverse transcription polymerase chain reaction and Western blot analyses. AQP function was determined by cell swelling and apoptotic assays in the absence and presence of HgCl(2) , a non-specific AQP inhibitor. Results: In this study, we report that activated HSCs showed no detectable expression of AQP 1, 5, 8, 9 and 12 mRNAs but expression was observed in quiescent HSCs. Similarly, AQP 0, 1, 8 and 9 protein was not detected in activated HSCs but was measured in quiescent HSCs. Dual fluorescent immunohistochemistry confirmed that AQP expression is decreased in activated HSCs in a model of liver injury. Functional studies demonstrated that quiescent HSCs were highly susceptible to osmotic challenge and apoptotic stimulus, whereas activated HSCs were less responsive. Finally, apoptosis was abrogated by the inhibition of AQP-dependent water movement. Conclusions: These findings demonstrate that increased resistance to apoptosis in activated HSCs is due, at least in part, to the changes in AQP expression and function that occur following HSC activation.
MeSH term(s)	Animals ; Apoptosis/drug effects ; Aquaporins/antagonists & inhibitors ; Aquaporins/genetics ; Aquaporins/metabolism ; Blotting, Western ; Cell Membrane Permeability ; Cell Shape ; Cells, Cultured ; Fluorescent Antibody Technique ; Gene Expression Regulation ; Hepatic Stellate Cells/drug effects ; Hepatic Stellate Cells/metabolism ; Hepatic Stellate Cells/pathology ; Male ; Mercuric Chloride ; Osmosis ; RNA, Messenger/metabolism ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Time Factors ; Water/metabolism
Chemical Substances	Aquaporins ; RNA, Messenger ; Water (059QF0KO0R) ; Mercuric Chloride (53GH7MZT1R)
Language	English
Publishing date	2010-10-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2102783-3
ISSN	1478-3231 ; 1478-3223
ISSN (online)	1478-3231
ISSN	1478-3223
DOI	10.1111/j.1478-3231.2010.02356.x
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1632: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Nonmuscle myosin II regulates migration but not contraction in rat hepatic stellate cells

Cathy C Moore / Ashley M Lakner / Christopher M Yengo / Laura W Schrum

World Journal of Hepatology, Vol 3, Iss 7, Pp 184-

2011 Volume 197

Abstract: AIM: To identify and characterize the function of nonmuscle myosin II (NMM II) isoforms in primary rat hepatic stellate cells (HSCs). METHODS: Primary HSCs were isolated from male Sprague-Dawley rats by pronase/collagenase digestion. Total RNA and ... ...

Abstract	AIM: To identify and characterize the function of nonmuscle myosin II (NMM II) isoforms in primary rat hepatic stellate cells (HSCs). METHODS: Primary HSCs were isolated from male Sprague-Dawley rats by pronase/collagenase digestion. Total RNA and protein were harvested from quiescent and culture-activated HSCs. NMM II isoform (II-A, II-B and II-C) gene and protein expression were measured by RealTime polymerase chain reaction and Western blot analyses respectively. NMM II protein localization was visualized in vitro using immunocytochemical analysis. For in vivo assessment, liver tissue was harvested from bile duct-ligated (BDL) rats and NMM IIisoform expression determined by immunohistochemistry. Using a selective myosin II inhibitor and siRNA-mediated knockdown of each isoform, NMM II functionality in primary rat HSCs was determined by contraction and migration assays. RESULTS: NMM II-A and II-B mRNA expression was increased in culture-activated HSCs (Day 14) with significant increases seen in all pair-wise comparisons (II-A: 12.67 ± 0.99 (quiescent) vs 17.36 ± 0.78 (Day 14), P < 0.05; II-B: 4.94 ± 0.62 (quiescent) vs 13.90 ±0.85 (Day 14), P < 0.001). Protein expression exhibited similar expression patterns (II-A: 1.87 ± 2.50 (quiescent) vs 58.64 ± 8.76 (Day 14), P < 0.05; II-B: 1.17 ± 1.93 (quiescent) vs 103.71 ± 21.73 (Day 14), P < 0.05). No significant differences were observed in NMM II-C mRNA and protein expression between quiescent and activated HSCs. In culture-activated HSCs, NMM II-A and II-B merged with F-actin at the cellular periphery and throughout cytoplasm respectively. In vitro studies showed increased expression of NMM II-B in HSCs activated by BDL compared to sham-operated animals. There were no apparent increases of NMM II-A and II-C protein expression in HSCs during hepatic BDL injury. To determine the contribution of NMM II-A and II-B to migration and contraction, NMM II-A and II-B expression were downregulated with siRNA. NMM II-A and/or II-B siRNA inhibited HSC migration by approximately 25% compared to scramble siRNA-treated cells. Conversely, siRNA-mediated NMM II-A and II-B inhibition had no significant effect on HSC contraction; however, contraction was inhibited with the myosin II inhibitor, blebbistatin (38.7% ± 1.9%). CONCLUSION: Increased expression of NMM II-A and II-B regulates HSC migration, while other myosin IIclasses likely modulate contraction, contributing to development and severity of liver fibrosis.
Keywords	Hepatic stellate cells ; Nonmuscle myosin II ; Migration ; Contraction ; Blebbistatin ; Hepatic injury ; Diseases of the digestive system. Gastroenterology ; RC799-869 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Gastroenterology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	571
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	Baishideng Publishing Group Co., Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Discovery of YAP1/TAZ pathway inhibitors through phenotypic screening with potent anti-tumor activity via blockade of Rho-GTPase signaling.

Graham, Keith / Lienau, Philip / Bader, Benjamin / Prechtl, Stefan / Naujoks, Jan / Lesche, Ralf / Weiske, Joerg / Kuehnlenz, Julia / Brzezinka, Krzysztof / Potze, Lisette / Zanconato, Francesca / Nicke, Barbara / Montebaur, Anna / Bone, Wilhelm / Golfier, Sven / Kaulfuss, Stefan / Kopitz, Charlotte / Pilari, Sabine / Steuber, Holger /

Cell chemical biology

2024

Abstract: This study describes the identification and target deconvolution of small molecule inhibitors of oncogenic Yes-associated protein (YAP1)/TAZ activity with potent anti-tumor activity in vivo. A high-throughput screen (HTS) of 3.8 million compounds was ... ...

Abstract	This study describes the identification and target deconvolution of small molecule inhibitors of oncogenic Yes-associated protein (YAP1)/TAZ activity with potent anti-tumor activity in vivo. A high-throughput screen (HTS) of 3.8 million compounds was conducted using a cellular YAP1/TAZ reporter assay. Target deconvolution studies identified the geranylgeranyltransferase-I (GGTase-I) complex as the direct target of YAP1/TAZ pathway inhibitors. The small molecule inhibitors block the activation of Rho-GTPases, leading to subsequent inactivation of YAP1/TAZ and inhibition of cancer cell proliferation in vitro. Multi-parameter optimization resulted in BAY-593, an in vivo probe with favorable PK properties, which demonstrated anti-tumor activity and blockade of YAP1/TAZ signaling in vivo.
Language	English
Publishing date	2024-03-19
Publishing country	United States
Document type	Journal Article
ISSN	2451-9448
ISSN (online)	2451-9448
DOI	10.1016/j.chembiol.2024.02.013
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Opioid-like compound exerts anti-fibrotic activity via decreased hepatic stellate cell activation and inflammation.

Day, Stephani A / Lakner, Ashley M / Moore, Cathy C / Yen, Mao-Hsiung / Clemens, Mark G / Wu, Edwin S / Schrum, Laura W

Biochemical pharmacology

2011 Volume 81, Issue 8, Page(s) 996–1003

Abstract: Hepatic fibrosis is characterized by excess type I collagen deposition and exacerbated inflammatory response. Naltrexone, an opioid receptor antagonist used for treating alcohol abuse, attenuates hepatocellular injury in fibrotic animal models, which can ...

Abstract	Hepatic fibrosis is characterized by excess type I collagen deposition and exacerbated inflammatory response. Naltrexone, an opioid receptor antagonist used for treating alcohol abuse, attenuates hepatocellular injury in fibrotic animal models, which can be accompanied by deleterious side effects. Additionally, opioid neurotransmission is upregulated in patients with inflammatory liver disease. Several derivatives of Naltrexone, Nalmefene (Nal) and JKB-119, exert immunomodulatory activity; however, unlike Nal, JKB-119 does not show significant opioid receptor antagonism. To delineate the potential hepatoprotective effects of these compounds, we investigated if JKB-119 and Nal could modulate activation of hepatic stellate cells (HSCs), primary effector cells that secrete type I collagen and inflammatory mediators during liver injury. Our results demonstrated that Nal or JKB-119 treatment decreased smooth muscle α-actin, a marker of HSC activation, mRNA and protein expression. Despite decreased collagen mRNA expression, both compounds increased intracellular collagen protein expression; however, inhibition of collagen secretion was observed. To address a possible mechanism for suppressed collagen secretion or retention of intracellular collagen, endoplasmic (ER) protein expression and matrix metalloproteinase (MMP) activity were examined. While no change in ER protein expression (Grp78, PDI, Hsp47) was observed, MMP13 mRNA expression was dramatically increased. In an acute LPS inflammatory injury animal model, JKB-119 treatment decreased liver injury (ALT), plasma TNFα and PMN liver infiltration. Overall, these results suggest that JKB-119 can directly inhibit HSC activation attributed to anti-inflammatory activity and may, therefore, attenuate inflammation associated with HSC activation and liver disease.
MeSH term(s)	Actins/biosynthesis ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cells, Cultured ; Chemical and Drug Induced Liver Injury/drug therapy ; Chemical and Drug Induced Liver Injury/immunology ; Chemical and Drug Induced Liver Injury/metabolism ; Collagen/metabolism ; Disease Models, Animal ; Hepatic Stellate Cells/drug effects ; Hepatic Stellate Cells/immunology ; Hepatic Stellate Cells/metabolism ; Immunoblotting ; Liver Cirrhosis/drug therapy ; Liver Cirrhosis/immunology ; Liver Cirrhosis/metabolism ; Male ; Matrix Metalloproteinase 13/biosynthesis ; Matrix Metalloproteinase 2/biosynthesis ; Morphinans/pharmacology ; Morphinans/therapeutic use ; Naltrexone/analogs & derivatives ; Naltrexone/pharmacology ; Naltrexone/therapeutic use ; Narcotic Antagonists/pharmacology ; Narcotic Antagonists/therapeutic use ; Rats ; Rats, Inbred WKY ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction
Chemical Substances	Actins ; Anti-Inflammatory Agents, Non-Steroidal ; JKB 119 ; Morphinans ; Narcotic Antagonists ; smooth muscle actin, rat ; Naltrexone (5S6W795CQM) ; Collagen (9007-34-5) ; Matrix Metalloproteinase 13 (EC 3.4.24.-) ; Mmp13 protein, rat (EC 3.4.24.-) ; Matrix Metalloproteinase 2 (EC 3.4.24.24) ; Mmp2 protein, rat (EC 3.4.24.24) ; nalmefene (TOV02TDP9I)
Language	English
Publishing date	2011-04-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	208787-x
ISSN	1873-2968 ; 0006-2952
ISSN (online)	1873-2968
ISSN	0006-2952
DOI	10.1016/j.bcp.2011.01.015
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 19: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito