| Liver fibrosis is a common result of chronic hepatic injury of diverse causes.Studies performed in the recen years have brough sighfican insights in themechbosm and treatment about liver fibrosis. Hepacytes and hepatic stellate cells(HSC) are presently regarded as the key cells involved in the progression of liverfibrosis. Hepacyte necrosis is an initiating and sustaining stimulus in the process.HSC activation is considered to be the critical event in early hepatic fibrosis.Classically, fibrosis is described in terms of markedly increased produchon andunbalanced degradation ofextracelltilar matrix (ECM). Many diseases may lead toliver injury and viral infechon is main cause in our counny. However, there is noany effective therapies for it. So, it is very important to prevent hepatic fibrosis.Decorin belongs to a member of the expanding gene family encoding thesecreted, small, leucine-rich proteoglycans (SLRPs) that affect matrix assemblyand cellular growth. Decorin has been implicated in the prevention of renal andlung fibrosis and its cDNA was recently used as a novel gene therapy tool fortreatment of fibrotic diseases caused by TGF β.Gressner and Gallai et al.have investigated the distribution and 1ocation ofdecorin in liver under the physiological and pathophysiological conditions as wellas expression of decorin mRNA in animal model by immunohistochemistry andanalysis of mRNA. In our country little investigation was done about therelationship between decorin and liver fibrosis. In this work the regulation ofdecorin on hepacytes (L-02) and hepatic stel1ate cells (HSC-T6) at cellular andgenetic level in vitro has been studied. Furthrmore, we have examined theeffects of some cytokines on the expression of the gene encoding decorin incultured HSC-T6 cells. Our results suggested that decorin not only suppress theproliferation of hepacytes and HSC, make cells rnst in G, phase of cell cycle,but also indue aPoptOsis of them. It was concluded that decorin potentially offersa novel Phannacological intervention that could be useful in bent liverfibrosis.l. Effect8 of decorin on the proliferation of L-02 and HSC-T6cellsDuring L-02 and HSC-T6 cells cultUred with decorin in different dose(5,l0u g/IIil) and the(2-6days), we have detedned the cell numbers,the amoUns of3H-TdR and sH-Leu incorporatiPn, and analyzed the variations of cel1 cycles. Thecell growh was retarded markedly: l) the cell number, the cell proliferation rateand the axnoUnts of,H-TdR uPtake of these cel1s wee decreased compared withcontrol at day 4 to 6 (P<0.0l). The percentae of G, Phase was increased (l9.6%and 29.08% higher than control), Whereas the percentage of S phase wasdecreased sighficanhy (18.45% and 20.98% lowe than control) and cells in Gzphase were reduced even absen. These resultS showed that decorin ndgh be acomPoneni of negative loop tha contrOls cell proliferation.ms is associated withcell arrest in G, phase and suPPression of DNA synthsis. Decorin exerts adifferent effect on the individual phase of cell cycle.2. Preliminary observation on apoptOsis of L-02 and HSC-T6cells induced by decorin.Both tWO cell lines wee culbed with decorin, the apoptosis was detected byobserving the changes in morphology, analysing the content of DNA by flowcytometry, wrEL labeling DNA-cleavage and by transmission e1ectron-tnicroscOPe identifing the characteristics of aPoPtosis. l) aPoptosis of L-02 andHSC-T6 cells could be efficiently induced by decorin (20-40u g/nil). with thepresence of aPoptotc changes in morphology, aPoPtotic peak before G, phase ofcell cycle or FCM displaying a characteristic pattCm of stutural changes inmembran and cytoplasm, including raPid blebbing of plasma membrane andnuclear disintegration, chrOmatin condensation and aPOPotic bodies formations,but negative to twan blue stalning. Apoptosis began to increase on day 2, reacheda Peak on day 4. The changes of aPoptosis increa...
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