Induction and coexpression of latent transforming growth factor beta-binding protein-1 and fibrillin-1 in experimental glomerulonephritis.
BACKGROUND
Latent transforming growth factor-beta-binding protein 1 (LTBP-1) and fibrillin-1 were shown to colocalize and interact in the extracellular matrix of the skin and vasculature. This interaction may regulate transforming growth factor-beta (TGF-beta) activity. TGF-beta is an important progression factor for glomerular diseases. We hypothesized that LTBP-1 and fibrillin-1 are coexpressed in the glomerulus and upregulated during glomerulonephritis.


METHODS
Acute anti-Thy1.1 glomerulonephritis was induced with a single intravenous injection (1 mg/kg body weight) of a monoclonal anti-Thy1.1 antibody in rats. Real-time RT-PCR and immunohistochemical analyses for LTBP-1 and fibrillin-1 were performed.


RESULTS
Induction of glomerular LTBP-1 mRNA was detected on day 2 of disease, while mRNA for fibrillin-1 was already upregulated 1 day after induction of disease. Both LTBP-1 and fibrillin-1 showed a mesangial distribution. An expansion of the LTBP-1 and fibrillin-1-positive mesangial area was seen on day 6 of disease, when transient matrix accumulation was most prominent. On day 12 of disease, glomerular LTBP-1 and fibrillin-1 immunoreactivities had returned to control levels. In serial sections, some colocalization of LTBP-1 and fibrillin-1 was detected in control as well as in nephritic glomeruli.


CONCLUSIONS
Mesangial expression of LTBP-1 and fibrillin-1 is induced early in experimental nephritis and LTBP-1 and fibrillin-1 are partially colocalized in the nephritic glomerulus. An interaction of these molecules could stabilize latent TGF-beta complexes and thus attenuate the activation of TGF-beta during this self-limited glomerular disease.
Porst
Markus
M
Children's Hospital, Erlangen, Germany.
Daniel
Christoph
C
Plank
Christian
C
Schocklmann
Harald O
HO
Reinhardt
Dieter P
DP
Hartner
Andrea
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000071838:Fibrillin-1; D000071837:Fibrillins; D005921:Glomerulonephritis / Q000276:immunology / Q000378:metabolism*; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism; D053779:Latent TGF-beta Binding Proteins; D008297:Male; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018800:Thy-1 Antigens / Q000276:immunology; D013997:Time Factors; D014018:Tissue Distribution; D015854:Up-Regulation; D054392:Adipokines
D000911:Antibodies, Monoclonal; D000071838:Fibrillin-1; D000071837:Fibrillins; D047908:Intracellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D008840:Microfilament Proteins; D012333:RNA, Messenger; D018800:Thy-1 Antigens; C000605725:Fbn1 protein, rat; D054392:Adipokines