Ja. Bassuk et al., Induction of TGF-beta 1 by the matricellular protein SPARC in a rat model of glomerulonephritis, KIDNEY INT, 57(1), 2000, pp. 117-128
Background. SPARC has been implicated as a counteradhesive and antiprolifer
ative protein associated with deposits of extracellular matrix in renal dis
ease.
Method. We have examined the effect of recombinant SPARC containing a C-ter
minal His tag (rSPARC) in an acute model of mesangial cell injury that is i
nduced in the rat by an antibody against the Thy1 antigen on the mesangial
cell membrane. The recombinant protein was administered 24 hours after the
induction of nephritis and was infused through day 4.
Results. rSPARC was localized to the renal glomeruli of rats treated with a
nti-Thy1 antibody. Type I collagen and fibronectin, as well as transforming
growth factor-beta 1 (TGF-beta 1), were increased at day 5 in rats treated
with rSPARC (N = 4, P < 0.05 vs. delivery buffer), but only minimal effect
s were seen on mesangial cell and endothelial cell proliferation. In primar
y cultures of rat mesangial cells, infusion of rSPARC was associated with i
ncreases in TGF-beta 1 mRNA and in total, secreted TGF-beta 1 protein.
Conclusions. rSPARC stimulates expression of TGF-beta 1 both in vitro and i
n vivo. Given the closely regulated expression of SPARC, TGF-beta 1, and ty
pe I collagen in several animal models of glomerulonephritis, we propose th
at SPARC could be one of the major mediators of the induction of TGF-beta 1
in renal disease.