[Effects of aldose reductase transfection on the proliferation of rat mesangial cells in vitro].
OBJECTIVE
To study the effects of aldose reductase (AR) on the proliferation of rat mesangial cells (MsC) in vitro and to investigate its mechanism.


METHODS
Cell proliferation was assessed by MTT colorimetric assay. Cell cycle and apoptosis were analyzed by flow cytometry. The growth of normal MsC and AR transfected MsC was compared. The proliferation of PDGF-BB and cellular growth stimulation by 10% NBS were investigated using AR inhibitors (ARI) Sorbinil and Zopolrestat. The effects of PDGF-BB on the expression of AR, p65 and c-Jun were assessed by Western blot. Activation of AP-1 was measured by EMSA.


RESULTS
AR expression of transfected MsC was distinctly higher than that of the control. Transfected MsC grew quicker than normal cells. ARI partially inhibited the proliferation of transfected MsC under the stimulation of PDGF-BB and 10% NBS, whereas 10% NBS had no effect on normal MsC. PDGF-BB upregulated the expression of AR and c-Jun, but had no effect on p65. The upregulation of c-Jun and the activation of AP-1 could be attenuated by ARI.


CONCLUSIONS
AR may participate in the pathological proliferation of MsC through the pathway related to the activation of AP-1.
Che
Qi
Q
Department of Pathology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Jiang
Tao
T
Lin
Yi-feng
YF
Li
Hui
H
Zhang
Nong
N
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000077214:Becaplermin; D052160:Benzothiazoles / Q000494:pharmacology; D002453:Cell Cycle; D049109:Cell Proliferation; D002478:Cells, Cultured; D005822:Genetic Vectors; D048289:Imidazolidines / Q000494:pharmacology; D050527:Mesangial Cells / Q000166:cytology / Q000378:metabolism*; D010793:Phthalazines / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014162:Transfection
D052160:Benzothiazoles; D048289:Imidazolidines; D010793:Phthalazines; D010982:Platelet-Derived Growth Factor; D016755:Proto-Oncogene Proteins c-jun; D020574:Proto-Oncogene Proteins c-sis; D018808:Transcription Factor AP-1; D000077214:Becaplermin; C067172:zopolrestat; D000449:Aldehyde Reductase; C026411:sorbinil