title: Aldose reductase regulates platelet-derived growth factor-induced proliferation             through mediating cell cycle progression in rat mesangial cells.
abstract: Aldose reductase (AR), the first and the rate-limiting enzyme of the polyol             pathway, has been implicated in platelet-derived growth factor (PDGF)-induced             proliferation of rat mesangial cells (MsCs). It is well known that AR plays an             important role in various chronic diabetic complications, for example, diabetic             nephropathy. Moreover, our previous studies have demonstrated that an AR inhibitor             (ARI) significantly reduced the proliferation of rat MsCs induced by PDGF, however,             the mechanism remains unclear. The aim of the present study was to elucidate the             molecular mechanisms through which AR regulates PDGF-induced rat MsC proliferation.             It was demonstrated that PDGF-induced MsC proliferation was significantly inhibited             by pretreatment with ARI. Cell cycle analysis by flow cytometry revealed that             ARI prevented the entry of cells from the G1 into the S phase. Furthermore, the             effect of the PI3K/Akt signaling pathway on the cell cycle was analyzed. The PI3K/Akt             pathway was activated with PDGF treatment. However, ARI blocked Akt activation             in response to PDGF. Moreover, PDGF increased the levels of p21Cip1 cyclin kinase             inhibitor protein in MsC, which was markedly inhibited by pretreatment with ARI.             Conversely, PDGF significantly reduced the levels of the p27Kip1 cyclin kinase             inhibitor protein, which was also restored by pretreatment with ARI. In conclusion,             AR is involved in PDGF-induced rat MsC proliferation, and may serve as a potential             target for the inhibition of MsC proliferation in several types of glomerulonephritis.
authors.affiliation: Department of Pathology, Huashan Hospital, Fudan University,                     Shanghai 200040, P.R. China.
authors.forename: Liping
authors.initials: L
authors.lastname: Zou
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Wang
authors.forename: Zude
authors.initials: Z
authors.lastname: Xu
authors.forename: Nong
authors.initials: N
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010793:Phthalazines / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism
chemical_list: D052160:Benzothiazoles; D050759:Cyclin-Dependent Kinase Inhibitor p21; D010793:Phthalazines; D010982:Platelet-Derived Growth Factor; D050760:Cyclin-Dependent Kinase Inhibitor p27; C067172:zopolrestat; D000449:Aldehyde Reductase; D019869:Phosphatidylinositol 3-Kinases; D020797:Receptor, Platelet-Derived Growth Factor beta; D051057:Proto-Oncogene Proteins c-akt