LIVER REGENERATION .1. THE EXTRACELLULAR-MATRIX IN HEPATIC REGENERATION

After partial hepatectomy, as a consequence of hepatocyte proliferatio n, cell clusters containing 10-14 hepatocytes are formed, These cluste rs are devoid of sinusoids and extracellular matrix; therefore, many h epatocytes are two to three cells removed from the vascular spaces, Fo ur days after hepatectomy, Ito cells send delicate cell processes betw een the hepatocytes in the clusters, This ''invasion'' of the clusters coincides with the activation in Ito cells of genes encoding for seve ral laminin chains, The penetration of Ito cells into the clusters is followed by fenestrated endothelial cells, and in this manner the norm al hepatocyte vascular relationship is restored, As soon as the normal vascular structure is reestablished, the laminin genes are turned off , This chain of events is similar to the one taking place during hepat ogenesis when continuous capillaries are converted into sinusoids, Thi s similarity in hepatogensis and regeneration suggests that the secret ed laminin chains may be signals for the vascularization of the cluste rs by fenestrated sinusoids, During this process neither entactin nor laminin a chains are secreted, The vascularization of the regenerating clusters contrasts sharply to the vascularization of cirrhotic nodule s, In the latter ease, entactin and perhaps laminin al chains are secr eted, and the final result is the formation of basement membranes and continuous capillaries rather than fenestrated sinusoids, We suggest t hat entactin and specific laminin chains play a crucial role in determ ining the outcome of hepatic injury, Definition of the roles of entact in and laminin chains in vascularization and modulation of the endothe lial phenotype will not only elucidate important aspects of regenerati on, but may provide a better understanding of cirrhosis and even sugge st therapeutic approaches.