Selective expression of TGF-beta2 and TGF-beta3 isoforms in early mesangioproliferative glomerulonephritis.
OBJECTIVE
Evidence from ex vivo glomerular analysis has implicated overexpression of transforming growth factor (TGF) beta 1 in progressive renal disease. The roles of TGF-beta2 and TGF-beta3 are less clear. The purpose of this study was to define the temporal expression and abundance of TGF-beta isoforms in both acute and progressive Thy-1 glomerulonephritis during the crucial initiation phase of these models.


METHODS
Acute Thy-1 glomerulonephritis was induced by a single injection of OX7, while the progressive model was induced by two injections, 7 days apart.


RESULTS
Cellular infiltration of glomeruli consisted of transient increases of neutrophils and ED1+ macrophages. The distribution of TGF-beta1, TGF-beta2, and TGF-beta3 revealed distinct differences in normal and nephritic rats. No changes in TGF-beta1 staining were observed within glomeruli of either model. In marked contrast, in the one-shot model, TGF-beta2 and TGF-beta3 stainings increased rapidly, yet transiently, throughout affected glomeruli, followed by more sustained staining in glomerular epithelial cells. Diffuse, transient staining was absent in two-shot glomerulonephritis, but an increase in epithelial cell staining mirrored that seen in the one-shot model.


CONCLUSIONS
Based on these results, we propose that the effects, formerly thought of as solely due to a single entity, TGF-beta1, may be the result of an interplay between individual TGF-beta isoforms.
Minto
Andrew W
AW
Section of Nephrology, Department of Medicine, University of Chicago, Chicago, Ill 60637, USA. aminto@uchicago.edu
Wilson
Heather M
HM
Rees
Andrew J
AJ
Quigg
Richard J
RJ
Brown
Paul A J
PA
D000208:Acute Disease; D000818:Animals; D002465:Cell Movement; D018450:Disease Progression; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D015432:Glomerulonephritis, Membranoproliferative / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007962:Leukocytes / Q000276:immunology; D008297:Male; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3
D020033:Protein Isoforms; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; C509046:Tgfb3 protein, rat; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3