INDUCTION OF PROCOLLAGEN TYPE-I GENE-EXPRESSION AND SYNTHESIS IN HUMAN HEPATIC STELLATE CELLS BY 4-HYDROXY-2,3-NONENAL AND OTHER 4-HYDROXY-2,3-ALKENALS IS RELATED TO THEIR MOLECULAR-STRUCTURE

4-Hydroxy-2,3-nonenal (HNE) has been shown to induce procollagen type I gene expression and synthesis in hepatic stellate cells (HSC), i.e. the cells responsible for deposition of collagen and other extracellul ar matrix proteins in fibrotic liver. Here we report that the stimulat ory effect of HNE mostly depends on the contemporary presence of the h ydroxyl group in position C-4 and of the double bond between position C-2 and C-3 since equimolar concentrations of 2,3-nonenal as well as o f nonanal did not affect procollagen type I synthesis either at mRNA o r at protein levels. Accordingly to this concept, all the other 4-hydr oxy-2,3-alkenals of different chain length rested on cultured human HS C (4-hydroxy-2,3-hexenal, 4-hydroxy-2,3-octenal and 4-hydroxy-2,3-unde cenal) strongly induced procollagen type I gene expression and synthes is. The stimulatory effect of 4-hydroxy-2,3-alkenals may depend on the well known ability of these aldehydes to react with either SH-groups or NH2-groups of functional proteins. (C) 1996 academic Press, Inc.