title: The expression of intermediate filament protein nestin and its association with cyclin-dependent kinase 5 in the glomeruli of rats with diabetic nephropathy.
abstract: BACKGROUND
  Podocyte injury plays a crucial role in the development of diabetic nephropathy (DN), but its underlying mechanism remains poorly understood. Emerging evidences suggest that the cytoskeleton disruption is related to podocyte injury. The aim of this study was to investigate whether nestin, a cytoskeleton-associated intermediate filament protein, is involved in the development of DN.
  
  
  METHODS
  Rat diabetes was induced by intraperitoneal injection of streptozotocin. The renal histological changes were investigated by light microscopy and transmission electron microscopy. The location of nestin and vimentin in renal tissues was observed by immunohistochemistry. The protein or messenger RNA levels of nestin and cyclin-dependent kinase 5 (Cdk5) were detected by Western blot and real-time polymerase chain reaction. The relationship between nestin and vimentin was detected by co-immunoprecipitation.
  
  
  RESULTS
  Compared with controls, diabetic rats showed significant characteristics of renal damage. The expression of nestin and vimentin in the glomeruli was increased at the early stage of diabetes, which then gradually decreased. Co-immunoprecipitation assays demonstrated that nestin disassembled with vimentin in diabetic rats. The expression of Cdk5 was increased in a time-dependent manner in diabetic rats. The degree of albuminuria in diabetic rats was negatively correlated with nestin and positively correlated with Cdk5. Roscovitine, a Cdk5 inhibitor, reduced the degradation of nestin. Moreover, podocyte injuries were significantly ameliorated by treatment with roscovitine.
  
  
  CONCLUSIONS
  The intermediate filament protein nestin is associated with development of DN. Blockage of Cdk5 increases the level of nestin and attenuates renal damage, which would provide a useful target for DN therapy.
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shuxia
authors.initials: S
authors.lastname: Liu
authors.forename: Qingjuan
authors.initials: Q
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Hao
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Shi
authors.forename: Song
authors.initials: S
authors.lastname: Zhao
authors.forename: Huijun
authors.initials: H
authors.lastname: Duan
mesh_terms: D000818:Animals; D051360:Cyclin-Dependent Kinase 5 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications*; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D064231:Nestin; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000077546:Roscovitine; D013311:Streptozocin / Q000009:adverse effects; D014746:Vimentin / Q000378:metabolism
chemical_list: D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D047428:Protein Kinase Inhibitors; D011687:Purines; D014746:Vimentin; D000077546:Roscovitine; D013311:Streptozocin; D051360:Cyclin-Dependent Kinase 5; C495907:Cdk5 protein, rat