%0 Journal Article
%T Daily genetic profiling indicates JAK/STAT signaling promotes early hepatic stellate cell transdifferentiation
%A Ashley M Lakner
%A Cathy C Moore
%A Alyssa A Gulledge
%A Laura W Schrum
%J World Journal of Gastroenterology
%D 2010
%I Baishideng Publishing Group Co. Limited
%X 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, ¦Á-SMA, PDGFR and TGF¦ÂR.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.
%K Cluster analysis
%K Fibrosis
%K Genetic profile
%K Hepatic stellate cell
%K Interleukin-6
%U http://www.wjgnet.com/1007-9327/full/v16/i40/5047.htm