SPARC (secreted protein, acidic and rich in cysteine)-also known as osteonectin, BM-40, and 43K glycoprotein-is secreted by endothelial cells and fibroblasts in response to culture shock. SPARC has been found in 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 messenger RNA (-A).
Moreover, when compared with control specimens, significantly increased levels of SPARC &A were found in fibrotic livers from two animal models of liver disease: murine schistosomiasis and carbon tetrachloride-induced fibrosis in rats. Fibrotic human livers also had markedly increased levels of SPARC mRNA in comparison with normal livers. We also detected an increased production of SPARC protein in the liver of animals treated with carbon tetrachloride. By immunocytochemical analysis, SPARC protein was apparent in freshly isolated It0 cells. Hybridization studies showed Ito cells to be the main source of SPARC mRNA. Extracts from a Kupffer-endothelial cell fraction exhibited traces of SPARC transcript, but expression of SPARC mRNA was absent in extracts from freshly isolated hepatocytes. These studies demonstrate the increased expression of SPARC -a protein that modulates cell shape and disrupts cell-matrix interactions-during the initial stages of hepatic fibrosis. (HEPATOLOGY 1995;21:847-854.)
The final common pathway that occurs in all forms of liver fibrosis regardless of its cause is the increased deposition of extracellular matrix (ECM) proteins, such as collagens, proteoglycans, fibronectin, and a variety of glycoproteins.'.' The process that leads to abnormal Abbreviations: ECM, extracellular matrix; SPAFtC, secreted protein, acidic and rich in cysteine; Ig, immunoglobulin; mRNA, messenger RNA; cDNA, complementary DNA, TGF, transforming growth factor.