Linked Life Data

20023766

Source:http://linkedlifedata.com/resource/pubmed/id/20023766

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8-9
pubmed:dateCreated
2009-12-21
pubmed:abstractText
Hepatic stellate cells (HSCs) are a major cell type of the liver that are involved in liver homeostasis. Upon liver damage, HSCs exit their normally quiescent state and become activated, leading to an increase of their proliferation, production of abnormal extracellular matrix proteins (ECMPs) and inflammatory mediators, and eventually liver fibrosis and cirrhosis. Current in vitro approaches to identify components that influence HSC biology typically investigate one factor at a time and generally ignore the complex crosstalk among the myriad of components that comprise the microenvironments of quiescent or activated HSCs. Here we describe a high throughput screening (HTS) approach to identify factors that affect HSC biology. Specifically, we integrated the use of ECMPs and signaling molecules into a combinatorial cellular microarray technology platform, thereby creating comprehensive "microenvironments". Using this technology, we performed real-time simultaneous screening of the effects of hundreds of unique microenvironments composed of ECMPs and signaling molecules on HSC proliferation and activation. From these screens, we identified combinations of microenvironment components that differentially modulate the HSC phenotype. Furthermore, analysis of HSC responses revealed that the influences of Wnt signaling molecules on HSC fate are dependent on the ECMP composition in which they are presented. Collectively, our results demonstrate the utility of high-content, array-based screens to provide a better understanding of HSC biology. Our results indicate that array-based screens may provide an efficient means for identifying candidate signaling pathways to be targeted for anti-fibrotic therapies.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1757-9708
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
513-24
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Investigating the role of the extracellular environment in modulating hepatic stellate cell biology with arrayed combinatorial microenvironments.
pubmed:affiliation
Department of Bioengineering, University of California, San Diego, USA. dbrafman@ucsd.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural