EXPRESSION OF SPARC IN NORMAL AND FIBROTIC LIVERS

SPARC (secreted protein, acidic and rich in cysteine)-also known as os teonectin, BM-40, and 43K glycoprotein-is secreted by endothelial cell s and fibroblasts in response to culture shock. SPARC has been found i n association with tissues undergoing cell. proliferation, migration, and extracellular matrix-remodeling. We demonstrate that normal livers from humans, rats, and mice express substantial levels of SPARC messe nger RNA (mRNA). Moreover, when compared with control specimens, signi ficantly increased levels of SPARC mRNA were found in fibrotic Livers from two animal models of liver disease: murine schistosomiasis and ca rbon tetrachloride-induced fibrosis in rats. Fibrotic human livers als o had markedly increased levels of SPARC mRNA in comparison with norma l livers. We also detected an increased-production of SPARC protein in the liver of animals treated with carbon tetrachloride. By immunocyto chemical analysis, SPARC protein was apparent in freshly isolated Ito cells. Hybridization studies showed Ito cells to be the main source of SPARC mRNA. Extracts from a Kupffer-endothelial cell fraction exhibit ed traces of SPARC transcript, but expression of SPARC mRNA was absent in extracts from freshly isolated hepatocytes. These studies demonstr ate the increased expression of SPARC-a protein that modulates cell sh ape and disrupts cell-matrix interactions-during the initial stages of hepatic fibrosis.