Induction of TGF-beta1 by the matricellular protein SPARC in a rat model of glomerulonephritis.
Induction of TGF-beta1 by the matricellular protein SPARC in a rat model of glomerulonephritis.


BACKGROUND
SPARC has been implicated as a counteradhesive and antiproliferative protein associated with deposits of extracellular matrix in renal disease.


METHODS
We have examined the effect of recombinant SPARC containing a C-terminal His tag (rSPARC) in an acute model of mesangial cell injury that is induced 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 anti-Thy1 antibody. Type I collagen and fibronectin, as well as transforming growth factor-beta1 (TGF-beta1), were increased at day 5 in rats treated with rSPARC (N = 4, P < 0.05 vs. delivery buffer), but only minimal effects were seen on mesangial cell and endothelial cell proliferation. In primary cultures of rat mesangial cells, infusion of rSPARC was associated with increases in TGF-beta1 mRNA and in total, secreted TGF-beta1 protein.


CONCLUSIONS
rSPARC stimulates expression of TGF-beta1 both in vitro and in vivo. Given the closely regulated expression of SPARC, TGF-beta1, and type I collagen in several animal models of glomerulonephritis, we propose that SPARC could be one of the major mediators of the induction of TGF-beta1 in renal disease.
Bassuk
J A
JA
Department of Biological Structure, University of Washington School of Medicine, Seattle, Washington 98195-7420, USA. bassuk@u.washington.edu
Pichler
R
R
Rothmier
J D
JD
Pippen
J
J
Gordon
K
K
Meek
R L
RL
Bradshaw
A D
AD
Lombardi
D
D
Strandjord
T P
TP
Reed
M
M
Sage
E H
EH
Couser
W G
WG
Johnson
R
R
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D015676:Osteonectin / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics
D015676:Osteonectin; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta