Heparin reduces glomerular infiltration and TGF-beta protein expression by macrophages in puromycin glomerulosclerosis.
BACKGROUND
In a number of experimental models of nephropathy, heparin is renoprotective because it inhibits mesangial matrix synthesis and cell proliferation; in most of these models, glomerular macrophage infiltration has a pathogenic role. We investigated the hypothesis that heparin might also be renoprotective by modulating the macrophages in various ways in the chronic puromycin glomerulosclerosis model.


METHODS
We studied the effect of a 3 month course, two different dosages of a non-anticoagulant heparin by immunohistochemical evaluation of the number of macrophages (ED-1 positive cells) in glomeruli, as well as the expression and deposition of TGF-beta and latent TGF-beta binding protein in foam cells and mesangial matrix.


RESULTS
The renoprotective effect of heparin in this model was confirmed by our observation of lower urine protein and albumin excretion, and a reduced glomerular sclerosis score. These effects were associated with the prevention of macrophage glomerular infiltration, and the inhibition of the TGF-beta axes in foam cells as shown by the reduction in cytoplasm immunostaining for TGF-beta and LTBP-1; heparin also reduced peri-macrophagic collagen IV deposition.


CONCLUSIONS
The inhibition of TGF-beta in macrophages seems to be part of heparin general activities. The inhibitory effect of heparin on macrophage infiltration and TGF-beta synthesis in this renal disease model supports the notion that heparin and derived molecules constitute potentially useful therapeutic agents in nephropathies.
Ceol
Monica
M
Department of Medical and Surgical Sciences, Division of Nephrology, Policlinico Universitario, University of Padua, Via Giustiniani 2, 35128 Padua, Italy.
Vianello
Daniela
D
Schleicher
Erwin
E
Anglani
Franca
F
Barbanti
Miriam
M
Bonfante
Luciana
L
Bertaglia
Giselda
G
Graziotto
Romina
R
D'Angelo
Angela
A
Del Prete
Dorella
D
Gambaro
Giovanni
G
D000704:Analysis of Variance; D000818:Animals; D001707:Biopsy, Needle; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy* / Q000473:pathology*; D006493:Heparin / Q000494:pharmacology*; D007150:Immunohistochemistry; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011336:Probability; D011691:Puromycin; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000187:drug effects*
D016212:Transforming Growth Factor beta; D011691:Puromycin; D006493:Heparin