s-., ?? -??_-- '? Non-alcoholic steatohepatitis (NASH.)js directly correlated,with body.mass inde>?(B.MI).: iCryp^pgenic ,?.,_... cirrhosis (CC) is associated with NASH and obesity,,and all three.are independen.lrisk.factors for ,,_ hepatoceNular.carcinoma (HCC)..We,hope tojo.b.etter, understand factors inhejentt;^ste'atoticJivers^that predispose them to liyer disease,and develppmejntof H.CCi;.Jhe,,primary pbjeptLye of this.'pr.oposal is.tOv,,., examine the role of Toll-like,Receptor-4 (TLR4). signaling,jn^.the progression :of fatty.Jjyer disease IQ ,HpC. Using pathology, biochemistry, and mplecularbiology tools,,we will evaluate the.;expr.essionrpf,TLR4 complex in NASH and NASH-implicated human. HCC, .jnyesWgate..the effect)pf,moduJatin.g.TLR4.sign.ajing.on proliferative competency, and determjneJfJL.R4',.sjgn_aii;ng,is,necessary fqr,deyeloprnent,pf HCC in a murine model of NASH. We have deemedI TLR4 as the nexus of a signal pathway that ultimately leads to NASH and HCC in this experimental system. Should TLR4 fail to be the nexus, it may still be implicitly involved in hepatic disease progression, arid our research will clarify its role'in this process*^ * >
| Pierre, Ketsia B; Jones, Christopher M; Pierce, Janene M et al. (2009) NFAT4 deficiency results in incomplete liver regeneration following partial hepatectomy. J Surg Res 154:226-33 |
| Nicoud, Ian B; Jones, Christopher M; Pierce, Janene M et al. (2007) Warm hepatic ischemia-reperfusion promotes growth of colorectal carcinoma micrometastases in mouse liver via matrix metalloproteinase-9 induction. Cancer Res 67:2720-8 |
