Expression of fibronectin splice variants in the postischemic rat kidney

Using an in vivo rat model of unilateral renal ischemia, we previously show ed that the expression and distribution of fibronectin (FN), a major glycop rotein of plasma and the extracellular matrix, dramatically changes in resp onse to ischemia-reperfusion. In the distal nephron in particular, FN accum ulates in tubular lumens, where it may contribute to obstruction. In the pr esent study, we examine whether the tubular FN is the plasma or cellular fo rm, each of which is produced by alternative splicing of a single gene tran script. We demonstrate that FN in tubular lumens does not contain the extra type III A (EIIIA) and/or the extra type III B (EIIIB) region, both of whi ch are unique to cellular FN. It does, however, contain the V95 region, whi ch in the rat is a component of FNs in both plasma and the extracellular ma trix. Expression of FN containing EIIIA increases dramatically in the renal interstitium after ischemic injury and continues to be produced at high le vels 6 wk later. V95-containing FN also increases in the interstitial space , albeit more slowly and at lower levels than FN containing EIIIA; it also persists 6 wk later. FN containing the EIIIB region is not expressed in the injured kidney. The presence of V95 but not the EIIIA or EIIIB regions of FN in tubular lumens identifies the origin of FN in this location as the pl asma; tubular FN is ultimately voided in the urine. The data indicate that both plasma and cellular FNs containing the V95 and/or EIIIA regions may co ntribute to the pathogenesis of acute renal failure and to the repair of th e injured kidney.