The Receptor Recognition And Function Of CTGF In Human Hepatic Stellate Cells

Objective：The aims of the study were to detect the receptor recognitionand function of CTGF on human hepatic stellate cells.Further clarify that thehCTGF play an important role in human liver fibrosis.Background：CTGF is a C-terminal cysteine-rich secretory peptide, whichcontains349amino acids with a molecular weight of38KD. The encoding geneof the hCTGF is located on the long arm of chromosome6（6q23.1）, containsfive exons and four introns. Its biological activity mainly in promoting theproliferation of collagen synthesis, and regulate gene expression ofextracellular,mediated cell adhesion, stimulate cell migration, promotingangiogenesis, and promote the proliferation of cartilage and bone development,and induction of apoptosis. A lot of research based on animal experimentsindicate that CTGF is closely related to the liver fibrosis development, As forCTGF different biological species there are structural differences, so far widelyused in vitro and in rats to study the biological activity of CTGF can not reflectthe true role of hCTGF in human.Materials and Methods: cultured human hepatic stellate cells LX-2isunder in hCTGF stimulation to establish the appropriate cell model,The celladhesion, migration and proliferation assays were used for detecting hCTGFinduced hHSC adhesion, migration and proliferation function.The LX-2cellcycle progression by flow cytometry.Results：The results show that: Adhesion of hHSC cells to hCTGF wasseen in a dose-dependent manner with an optimal concentration of2μg/ml.Integrin αvβ3functions as a co-receptor with HSPGs for CTGF-mediatedHSC adhesion.Mg²⁺, Mn²⁺, especially Mn²⁺as a necessary Divalent cation participate in the process of adhesion.CTGF can promote cellmigration,proliferation of hepatic stellate cells.Besides,Cell cycle analysisshowed that hCTGF also increase process of hHSC cell cycle, leading toincreased number of cells in S phase. In addition, anti-CTGF antibody caneffectively antagonize the CTGF-induced adhesion, migration and proliferationfunctions.Conclusion：hCTGF can promote hHSC cell adhesion，intergrin αvβ3isone of the specific receptors in human hepatic stellate cell membrane surfacewhich mediated adhesion.Besides, hCTGF promote migration, proliferation andcell cycle progression of human hepatic stellate cells, This study showed thathCTGF play an important role in hHSC-mediated liver fibrosis at the cellularlevel.Targeting hCTGF may become a new target for the treatment of liverfibrosis.