title: Podocyte injury and glomerulosclerosis in hyperhomocysteinemic rats.
abstract: OBJECTIVE
  We previously reported that increase in plasma homocysteine (Hcys) levels by a 6-week methionine treatment produced remarkable glomerular injury. However, the mechanism by which hyperhomocysteinemia (hHcys) produces glomerular injury remains unknown. The present study was to observe when glomerular injury happens during hHcys and to explore the possible role of podocyte injury in the progression of glomerulosclerosis associated with hHcys.
  
  
  METHODS
  Uninephrectomized Sprague-Dawley rats treated with methionine were used to examine the time course of glomerular injury induced by hHcys.
  
  
  RESULTS
  Creatinine clearance was not different until rats were treated with methionine for 6 weeks, although plasma Hcys levels significantly increased at the 1st week of methionine treatment. However, urinary albumin excretion increased at the 2nd week of methionine treatment. Morphological examinations showed that mesangial expansion occurred at the 2nd week and podocyte effacement was also observed as processed glomerular damage during hHcys. Immunofluorescence analyses demonstrated that podocin and nephrin expressions were reduced, while alpha-actinin-4 increased during hHcys.
  
  
  CONCLUSIONS
  Increased plasma Hcys level is an important pathogenic factor resulting in glomerular injury even in the very early time of hHcys. These pathogenic effects of Hcys are associated with podocyte injury and changed expression and distribution of podocyte-associated proteins.
authors: Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors: Fan
authors: F
authors: Yi
authors: Elisabete A
authors: EA
authors: dos Santos
authors: Min
authors: M
authors: Xia
authors: Qi-Zheng
authors: QZ
authors: Chen
authors: Pin-Lan
authors: PL
authors: Li
authors: Ningjun
authors: N
authors: Li
mesh_terms: D000185:Actinin / Q000378:metabolism; D000419:Albuminuria; D000818:Animals; D003404:Creatinine / Q000652:urine; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D006710:Homocysteine / Q000097:blood; D020138:Hyperhomocysteinemia / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008715:Methionine; D008840:Microfilament Proteins / Q000378:metabolism; D050199:Podocytes / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: C491751:Actn4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; C407223:NPHS2 protein; C113267:nephrin; D006710:Homocysteine; D000185:Actinin; D008715:Methionine; D003404:Creatinine