Expression of fibronectin splice variants in the postischemic rat kidney.
Using an in vivo rat model of unilateral renal ischemia, we previously showed that the expression and distribution of fibronectin (FN), a major glycoprotein of plasma and the extracellular matrix, dramatically changes in response to ischemia-reperfusion. In the distal nephron in particular, FN accumulates in tubular lumens, where it may contribute to obstruction. In the present study, we examine whether the tubular FN is the plasma or cellular form, each of which is produced by alternative splicing of a single gene transcript. 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 which are unique to cellular FN. It does, however, contain the V95 region, which in the rat is a component of FNs in both plasma and the extracellular matrix. Expression of FN containing EIIIA increases dramatically in the renal interstitium after ischemic injury and continues to be produced at high levels 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 plasma; 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 contribute to the pathogenesis of acute renal failure and to the repair of the injured kidney.
Zuk
A
A
Department of Surgery, Beth Israel Deaconess Medical Center, Boston 02215, USA. azuk@caregroup.harvard.edu
Bonventre
J V
JV
Matlin
K S
KS
D058186:Acute Kidney Injury / Q000503:physiopathology*; D017398:Alternative Splicing / Q000502:physiology*; D000818:Animals; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005353:Fibronectins / Q000097:blood / Q000235:genetics* / Q000652:urine; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000502:physiology; D007511:Ischemia / Q000503:physiopathology*; D007536:Isomerism; D007672:Kidney Cortex / Q000737:chemistry / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000502:physiology; D014556:Urine / Q000737:chemistry
D016326:Extracellular Matrix Proteins; D005353:Fibronectins