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Interleukin‐6 as a Key Regulator for Early Hepatic Stellate Cell Transdifferentiation
Author(s) -
Moore Cathy C.,
Lakner Ashley M.,
Gulledge Alyssa A.,
Schrum Laura W.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.981.5
Subject(s) - transdifferentiation , hepatic stellate cell , biology , phenotype , signal transduction , fibrosis , transforming growth factor , microbiology and biotechnology , gene , endocrinology , medicine , stem cell , genetics
Hepatic stellate cell (HSC) transdifferentiation is critical to the development of fibrosis. Phenotypic changes have been documented over the course of HSC activation; however, little information is known about daily genetic alterations. In this study we examined the expression profile of 21 genes from freshly isolated HSCs and across 10 days in culture that are important mediators of HSC activation and fibrosis by RealTime PCR and clustered the data using AMADA software. By examining specific gene activation/inhibition as well as the rise and fall of expression across time, we identified distinct markers for quiescence (GFAP and PPARγ), early and late activation (SMA, desmin, MMP‐13, IL‐6), and fibrosis (collagen, TGFβ, TGFβR and PDGFR). Our results indicated an early transient spike in the IL‐6 signaling pathway. Therefore, we chemically blocked this pathway using JAK‐2 (AG490) and p38MAPK (SB203580) inhibitors to determine if genotypic alterations correlated to changes in activation as assessed morphologically. Our results demonstrated that inhibition of JAK‐2, but not p38MAPK, impeded the progression of early HSC activation. Overall, genetic and morphological observations showed that IL‐6 signaling may be a key factor for initiation of HSC transdifferentiation. Supported by NIH Grant AA14891.