Human DDR2 Stable Cell Line - CHO-K1

The mechanism by which type I collagen activates hepatic stellate cells during liver injury is unknown.DDR2 mRNA and protein are induced in stellate cells activated during liver injury in primary culture or in vivo.The receptor undergoes tyrosine phosphorylation in response to endogenous or exogenous type I collagen,whereas its expression is downregulated during growth-induced cytostasis on Matrigel.Some investigators have developed stellate cell lines that stably overexpress wild-type DDR2,constitutively active chimeric DDR2 receptor(Fc-DDR2),truncated receptors expressing extracellular structural domains,or kinase-dead DDR2.DDR2 overexpressing cells had an increased ability to proliferate and invade Matrigel and these activities were directly correlated with increased expression of active matrix metalloproteinase 2(MMP-2).DDR2 was induced during stellate cell activation and suggests that the phosphorylated receptor is a mediator of MMP-2 release and stimulated growth in response to type I collagen.Furthermore,type I collagen-dependent upregulation of DDR2 expression establishes a positive feedback loop in activated stellate cells,leading to further cell proliferation and enhanced invasive activity.

Figure 1.Increased TlMP-2 or the MMP inhibitor GM6001 are required to inhibit proliferation of stellate DDR2 overexpressing cells.(a)HSC-T6 cells expressing GFP alone(control)or the constitutively active Fc-DDR2 were cultured for 48 hours in DMEM with 1%FCS in the presence of recombinant TlMP-2 or GM6001,10μM(GM).Incorporation of[3H]-thymidine during the last 6 hours of the experiment was measured.(b)TlMP-2 and MT1-MMP expression were analyzed by Western blots in the serum-free supernatants,or in the lysates fromHSC-T6 cells expressing GFP alone(control),or Fc-DDR2.(Olaso,Eet al.2001)