PMID- 23859838
OWN - NLM
STAT- MEDLINE
DCOM- 20140324
LR  - 20130830
IS  - 1095-9319 (Electronic)
IS  - 0026-2862 (Linking)
VI  - 89
DP  - 2013 Sep
TI  - Folic acid attenuates hyperhomocysteinemia-induced glomerular damage in rats.
PG  - 146-52
LID - S0026-2862(13)00103-9 [pii]
LID - 10.1016/j.mvr.2013.07.002 [doi]
AB  - The present study investigated whether lowering plasma homocysteine (Hcy) with 
      folic acid (FA) could attenuate hyperhomocysteinemia (HHcy)-associated glomerular 
      damage and possible mechanisms. The HHcy animal model was established by 
      intragastric administration with l-methionine in rats. FA was also given 
      intragastrically. Plasma Hcy and creatinine and urinary albumin were measured. 
      Histological and ultrastructural changes were observed by light and electron 
      microscopes. The expression of alpha-smooth muscle actin (alpha-SMA), proliferating 
      cell nuclear antigen (PCNA) and transforming growth factor-beta1 (TGF-beta1) in the 
      kidney was examined by immunohistochemical staining and western blot analysis. 
      The administration of l-methionine induced HHcy in rats. The HHcy rats developed 
      glomerulosclerosis and fibrosis. Plasma creatinine concentration and urinary 
      albumin excretion were also significantly increased in HHcy rats. Effacement and 
      extensively fusion of podocyte foot process was observed in HHcy rats, which was 
      associated with decreased expression of nephrin protein in renal cortex of HHcy 
      rats. Supplementation with FA lowered plasma Hcy significantly. Plasma creatinine 
      concentration and urinary albumin excretion were also significantly attenuated by 
      FA. Morphologically, HHcy-associated glomerulosclerosis, fibrosis, podocyte foot 
      process effacement and loss of podocyte nephrin, were significantly improved by 
      FA. The expressions of alpha-SMA, PCNA and TGF-beta1 were increased in renal cortex of 
      HHcy rats, and which were also partially reversed by FA. These data suggest that 
      elevated plasma Hcy is an important pathogenic factor for glomerular damage. 
      Lowering plasma Hcy by FA can inhibit TGF-beta1 expression and attenuate 
      HHcy-induced glomerular damage.
CI  - (c) 2013.
FAU - Cao, Lu
AU  - Cao L
AD  - Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen 
      University, Guangzhou 510080, PR China.
FAU - Lou, Xiaoying
AU  - Lou X
FAU - Zou, Zhaoxia
AU  - Zou Z
FAU - Mou, Nana
AU  - Mou N
FAU - Wu, Weikang
AU  - Wu W
FAU - Huang, Xiongqing
AU  - Huang X
FAU - Tan, Hongmei
AU  - Tan H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130713
PL  - United States
TA  - Microvasc Res
JT  - Microvascular research
JID - 0165035
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 9007-34-5 (Collagen)
RN  - 935E97BOY8 (Folic Acid)
RN  - AYI8EX34EU (Creatinine)
SB  - IM
MH  - Albuminuria/metabolism
MH  - Animals
MH  - Cell Proliferation
MH  - Collagen/chemistry
MH  - Creatinine/metabolism
MH  - Folic Acid/*pharmacology
MH  - Gene Expression Regulation
MH  - Homocysteine/metabolism
MH  - Hyperhomocysteinemia/*drug therapy/*metabolism
MH  - Immunohistochemistry
MH  - Kidney/*drug effects
MH  - Kidney Cortex/metabolism
MH  - Kidney Diseases/metabolism/pathology
MH  - Kidney Glomerulus/*metabolism
MH  - Podocytes/cytology
MH  - Random Allocation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Transforming Growth Factor beta1/metabolism
MH  - Up-Regulation
EDAT- 2013/07/19 06:00
MHDA- 2014/03/25 06:00
CRDT- 2013/07/18 06:00
PHST- 2013/05/31 00:00 [received]
PHST- 2013/07/03 00:00 [revised]
PHST- 2013/07/06 00:00 [accepted]
PHST- 2013/07/18 06:00 [entrez]
PHST- 2013/07/19 06:00 [pubmed]
PHST- 2014/03/25 06:00 [medline]
AID - S0026-2862(13)00103-9 [pii]
AID - 10.1016/j.mvr.2013.07.002 [doi]
PST - ppublish
SO  - Microvasc Res. 2013 Sep;89:146-52. doi: 10.1016/j.mvr.2013.07.002. Epub 2013 Jul 
      13.