Expression of collagen genes in the liver.


Hepatic production of type I collagen is markedly increased in liver cirrhosis. Previous studies using primary liver cell cultures have demonstrated that hepatocytes, lipocytes and endothelial cells are all capable of producing collagen. In this study in situ hybridization and hepatic cell sorting have been used to identify which cells are expressing the type I collagen gene, alpha 1(I), in normal rat liver. Northern blotting of mRNAs from purified hepatic cell populations demonstrated that both hepatocytes and several types of non-parenchymal cells express the collagen alpha 1(I) gene. Calculations based on cell numbers, yields of mRNA, and cellular mRNA concentration demonstrated that the majority of collagen alpha 1(I) mRNA originates from the hepatocytes in the normal liver. Localization of a collagen alpha 1(I) mRNA by in situ hybridization confirmed that both hepatocytes and non-parenchymal cells express this gene. Furthermore, collagen alpha 1(I) gene expression in hepatocytes was obtained by transfecting a reporter gene driven by the collagen alpha (I) 5' regulatory segment in primary liver cell cultures. Future experiments will further characterize the regulation of collagen alpha 1(I) gene expression in the liver.


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