REGULATION OF FIBRONECTIN EXPRESSION IN RAT REGENERATING LIVER

Fibronectin (FN) expression displays a complex regulation that results in precisely defined isoform patterns during different developmental stages, ageing and injury. The qualitative and quantitative changes that are observed derive from modulation of the rate of transcription of the single FN pre-mRNA and its specific differential processing in the EIIIA, EIIIB and V regions of rat FN. The liver is the major source of plasma FN which is characterised by the absence of the EIIIA and EIIIB exons. Here we show that in the rat regenerating liver there is a significant reprogramming of the splicing machinery that results in the synthesis by the liver of up to 17% of EIIIA+ FN linked with all the three V forms. On the other hand the EIIIB+ form is totally absent both in normal and regenerating liver. Furthermore there is a variation of the V pattern observed in the regenerating tissue, the V120 form (linked to both EIIIA+ and EIIIA- messengers) increases from 11 to 32%. The quantitative RT-PCR method was used to estimate the FN transcription rate, before and after partial hepatectomy. We have shown a 3-fold increase in FN mRNA in liver that is specifically linked to the regeneration process and not to the surgical stress.