Negative regulatory effects of somatostatin and its analogue on the extracellular matrixes metabolism in hepatic stellate cells / 中国病理生理杂志

ABSTRACT

AIM:To evaluate the negative regulatory effects of somatostatin(SST) and octreotide(OCT) on the extracellular matrixes(ECM) metabolism in rat hepatic stellate cells(HSCs).METHODS:HSCs were treated with different concentrations of SST or OCT.The mRNA levels of collage type I,III and the intracellular expression of collagen,matrix metalloproteinase-1(MMP-1),tissue inhibitor of metalloproteinase-1(TIMP-1) in activated HSCs were assessed by in situ hybridization(ISH),[3H]-proline incorporation and immunocytochemistry,respectively.In addition,levels of hyaluronic acid(HA),laminin(LM),and procollagen type III(PCIII) in the culture supernatant of HSCs were also detected by enzyme-linked immunosorbent assay.RESULTS:Both SST(10-7 mol/L-10-6 mol/L) and OCT(10-7 mol/L-10-5 mol/L) markedly down-regulated the transcription of collagen type I,III,and the production of collagen,HA,LM,PCIII in HSCs in a dose-dependent manner.Furthermore,HSCs treated with SST(10-6 mol/L) and OCT(10-6 mol/L-10-5 mol/L) significantly reduced TIMP-1 level,which resulted in an elevated ratio of MMP-1/TIMP-1.CONCLUSION:SST and its analogy inhibit the synthesis of ECM and enhance its degradation both at transcriptional and translational levels.