Expression of fibronectin mrna splice variants by rabbit lung in
vivo and by alveolar type ii cells in vitro.
Maniscalco, William M., Richard H. Watkins, Maura H. Campbell.
Department of Pediatrics, Division of Neonatology, Strong
Children's Research Center, University of Rochester, Rochester,
NY
APStracts 3:0158L, 1996.
Fibronectin (FN) is a multidomain glycoprotein with putative functions
in tissue development and repair. In repair of alveolar injury, FN
may promote the transition of type II epithelial cells to type I
epithelial cells. Alternative splicing of FN mRNA, including the
EIIIA and EIIIB exons, results in protein isoforms that have cell,
tissue and developmental specificity. The present work found that FN
mRNA with the EIIIA exon was in fetal, adult and oxidant-injured
rabbit lung. The EIIIB splice variant, however, was restricted to
fetal lung and adult lung recovering from oxidant injury. Because
alveolar type II cells in vitro express FN, we examined the splice
variants in two conditions that induce FN: TGF-[beta]1 treatment and
time in culture. TGF-[beta]1 increased both EIIIA and EIIIB mRNA
abundance by 10 fold. Increased EIIIA isoform immunostaining was also
noted. Type II cells that spontaneously express FN at 72 hrs in vitro
had increased EIIIA and EIIIB mRNA and increased immunostaining for
EIIIA. Nuclear run-off showed induction of FN gene transcription at
72 hrs in vitro. Together, these data show differential FN splice
variant expression in lung, with EIIIB mRNA restricted to fetal and
recovering, oxidant-injured lung. Furthermore, the transition of type
II cells to a type I-like cell is accompanied by increased FN gene
transcription and induction of both EIIIA and EIIIB mRNA.
Received 20 May 1996; accepted in final form 12 August 1996.
APS Manuscript Number L143-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 7 October 1996