Analysis of the linkage between fibronectin alternative spliced sites during ageing in rat tissues

The modulation of fibronectin (FN) functions in cell-cell and cell-substrate interactions in a variety of physiological situations is achieved by the selective expression of different isoforms, which in the rat are generated by alternatively splicing of at least three regions of the molecule: EIIIA, EIIIB and V. Extensive information has been collected on the regulation of the differential processing of the single alternatively spliced regions but up to now there was scant knowledge about a possible coordinated expression of the three regions in the same transcript. Using a long range RT-PCR system we have shown that most of the splicing regulation is autonomous for each individual region but we have also observed a preferential expression of the EIIIA+ form linked to the EIIIB- variant that is age independent. Furthermore the analysis of the single regions showed interesting variations occurring in brain during the ageing. There is a decrease in the V120 form between the 6- and the 24-month-old rat brain (from 57% to 39%), whereas despite a constant prevalence of the EIIIA- form in the young rats (65%) there is a random individual variation of this form in the old animals. Noteworthy no variations have been detected in the EIIIB region (90% EIIIB-). These data suggest a role for the V and EIIIA regions, but not for the EIIIB, during the ageing process at least in brain, since no variations were detected in kidney between the 6- and 24-month-old animals.