Glomerular epithelial cell injury accelerates the progression of antibody-induced mesangial proliferative nephritis.
BACKGROUND
Anti-Thy-1.1 antibody induces mesangioproliferative glomerulonephritis; however, the mesangial lesion is spontaneously recovered to the normal feature. Glomerular epithelial cells (GECs) play a crucial role in the glomerular function. Very little is known about the involvement of GECs in this disease model. This study is designed to investigate whether GEC injury prolongs the mesangial lesion.


METHODS
The effects of GEC damage on mesangioproliferative nephritis were studied with combined treatment using puromycin aminonucleoside (PAN) and monoclonal antibody (MAb) against rat mesangial Thy-1.1. Urinary protein, BUN, Pcr and Ccr were measured. To clarify the underlying mechanisms, morphological study and immunohistochemistry for alpha-SMA, FGF-2 and PCNA were carried out.


RESULTS
Simultaneous administration of PAN plus MAb induced progressive mesangioproliferative nephritis compared to PAN or MAb alone. Rats with combined treatment displayed renal dysfunction with massive proteinuria. Morphological studies showed that the glomeruli in combined group had features resembling those of progressive mesangial proliferative glomerulonephritis in humans. Morphologic lesions of GECs in acute nephritic phase were severer than those in other groups. Immunohistochemistry revealed that glomeruli of combined treatment exhibited persistent overexpression of alpha-SMA and FGF-2.


CONCLUSIONS
Simultaneous dysfunction of GECs and mesangial cells can lead to persistent glomerular perturbations with prolonged phenotypic change of mesangial cells, resulting in end-stage renal deficiency. GEC damage during the acute nephritic phase contributes to the progression of irreversible renal disease.
Shinosaki
Toshihiro
T
Shionogi Discovery Research Laboratories, Shionogi & Co., Toyonaka, Osaka, Japan. toshihiro.shinosaki@shionogi.co.jp
Notoya
Mitsuru
M
Nomura
Yasuharu
Y
Miyai
Ikuko
I
Kobayashi
Tatsuo
T
Kurihara
Hidetake
H
D000818:Animals; D002455:Cell Division / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology; D005920:Glomerular Mesangium / Q000276:immunology / Q000473:pathology*; D005921:Glomerulonephritis / Q000276:immunology / Q000473:pathology*; D007518:Isoantibodies / Q000494:pharmacology; D007676:Kidney Failure, Chronic / Q000276:immunology / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D007518:Isoantibodies; C035678:anti-Thy antibody