In vivo Collagen Synthesis and Deposition in Fibrotic and Regenerating Rat Livers

Abstract

The content of liver collagen increases during regeneration posthepatectomy as well as during scar formation after chronic administration of CC14. However, while in the former system restitution at integrum of the liver is obtained and a normal ratio of connective tissue to cellular elements is established, in the later condition homeostasis is lost and an absolute increase in connective tissue takes place. Therefore, it was important to determine if this difference was associated with differences in the amount and types of collagen produced and deposited in vivo. In this communication we describe experiments performed to determine the amount of collagen types I, III and V present in the connective tissues prepared from control and experimental animals, and to measure the extent of radioactivity in each collagen type after an in vivo pulse with tritiated proline. Our results showed that 5 days post-hepatectomy the net collagen content per g of fresh liver decreased to 50% of control values, the predominant collagen was type I, and the ratio of type I/III collagen was increased as compared to normal liver; in addition, a relative increase in type V collagen (23.6%) as compared to control animals (6.6%) was also seen. At 11 days post-hepatectomy, the amount of collagen per g of tissue increased to normal values, the ratio of type I/III collagen decreased due to an increase in type III collagen, and the amount of type IV collagen decreased to 12.8%. In the cirrhotic liver the net collagen content showed a five-fold increase, and the predominant collagen present in the extracellular matrix was type I collagen. The amount of radioactivity in collagens deposited into the extracellular matrix of normal, regenerating and fibrotic livers closely followed the percent concentration of liver collagen types. Our results suggest that collagens produced during tissue growth are those needed for remodeling and therefore they may be synthesized by the regenerating cells, mainly parenchyma) and endothelial cells. In fibrosis, the predominant collagen is type I, and accordingly, it may be produced preferentially by the fibroblastic cells that are increased in number in the injured liver.