Podocyte injury and glomerulosclerosis in hyperhomocysteinemic rats.
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.
Yi
Fan
F
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA.
dos Santos
Elisabete A
EA
Xia
Min
M
Chen
Qi-Zheng
QZ
Li
Pin-Lan
PL
Li
Ningjun
N
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
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