Role of Acetaldehyde on PDGF-BB-induced HSC Migration and Proliferation.

肝损伤伴随着肝星状细胞（HSC）转分化（活化）为肝星状细胞（HSC）。 肌成纤维细胞是肝纤维化中的关键事件，导致增殖和迁移增加。这些 事件伴随着细胞所需的细胞外基质成分的产生的改变， 基质相互作用和瘢痕组织的过度产生，包括I型胶原和纤连蛋白。因此，在本发明中， HSC转分化的抑制可以防止随后导致胶原过量的事件 沉积、纤维化和肝硬化。HSC活化的一个标志是血小板衍生生长的上调 因子-β受体（PDGF-betaR）及其对PDGF-BB的增加的迁移和增殖反应。 虽然许多研究都集中在PDGF-BB依赖的分子事件导致细胞增殖 和迁移，很少有人知道乙醛，乙醇的第一代谢产物，对PDGF的作用， β R表达和HSC增殖和迁移。此外，ACH和PDGF-BB对HSC- 基质相互作用仍有待研究。根据我们以前的研究，即乙醛 通过活性氧物质（过氧化氢）的积累发挥一些作用， 在本申请中提出的初步结果中，我们提出研究分子机制， 乙醛调节HSC中PDGF-β R的表达。我们亦会研究认可交收机构在 HSC对PDGF-BB的迁移和增殖反应以及PDGF-BB依赖的HSC中 细胞-基质相互作用我们的长期目标是解开乙醛引发的关键分子事件， 可以导致治疗干预，从而预防和/或改善酒精诱导的肝损害。 纤维化和肝硬化。

Liver injury is accompanied by trans-differentiation (activation) of hepatic stellate cells (HSC) into myofibroblasts, a key event in liver fibrogenesis that results in increased proliferation and migration. These vents are accompanied by alterations in the production of extracellular matrix components required for cell- matrix interactions and excess production of scar tissue, including type I collagen and fibronectin. Thus, nhibition of HSC trans-differentiation could prevent the subsequent events leading to excess collagen deposition, fibrosis and cirrhosis. A hallmark of HSC activation is the up-regulation of platelet-derived growth factor-beta receptor (PDGF-betaR) and their increased migratory and proliferative response to PDGF-BB. Although many studies have focused on PDGF-BB-dependent molecular events leading to cell proliferation and migration, little is known regarding the role of acetaldehyde, the first metabolite of ethanol, on PDGF- betaR expression and HSC proliferation and migration. Moreover, the role of ACH and PDGF-BB on HSC- matrix interactions remains to be investigated. Based on our previous studies, namely that acetaldehyde exerts some of its action via the accumulation of reactive oxygen species (hydrogen peroxide) and the preliminary results presented in this application we propose to investigate molecular mechanismswhereby acetaldehyde modulates the expression of PDGF-betaR in HSC. We will also study the role of ACH on the migratory and proliferative responses of HSC to PDGF-BB and on the PDGF-BB-dependent alterations in cell-matrix interactions. Our long term goal is to unravel key molecular events triggered by acetaldehyde that could lead to therapeutic intervention and thus, to prevention and/or amelioration of alcohol-induced liver fibrosis and cirrhosis.