OSTEONECTIN (SPARC) EXPRESSION IN HUMAN LIVER AND IN CULTURED HUMAN LIVER MYOFIBROBLASTS

Osteonectin/SPARC is a glycoprotein involved in the regulation of cell shape, adhesion, migration, and proliferation. It also has complex ef fects on extracellular matrix synthesis and turnover. We found that os teonectin mRNA was very abundant in a human Liver myofibroblast librar y. Using Northern and Western blot, immunoprecipitation, and radioimmu noassay, we found that cultured liver myofibroblasts actively secreted osteonectin. Myofibroblasts are very rare in normal liver but prolife rate during liver fibrosis where they synthesize extracellular matrix components. Thus, we studied the distribution of osteonectin in normal and fibrotic human liver using in situ hybridization. Osteonectin mRN A expression was weak in normal liver but very high in fibrotic liver within fibrous septae and scattered sinusoidal cells. Serial sectionin g and double staining experiments with an antibody to smooth muscle al pha-actin showed that osteonectin transcripts were mostly co-localized with myofibroblasts. In conclusion, osteonectin is highly expressed i n human liver myofibroblasts in culture as well as in human liver fibr osis in vivo. The many biological properties of osteonectin make it a candidate effector of human liver fibrogenesis.