[Losartan inhibits high glucose-induced CTGF expression via ERK1/2 MAPK pathways in mouse mesangial cells].
OBJECTIVE
To investigate the effects and mechanism of losartan on expression of CTGF induced by high glucose.


METHODS
Mouse mesangial cells (MMCs) were cultured in vitro, initially, MMCs were stimulated by high glucose(25 mmol/L glucose) for 24 h, 48 h, 72 h, the phosphorylation of ERK1/2 was assessed by Western blot. Then MMCs were randomly divided into 5 groups: (1) Low glucose group (5.6 mmol/L glucose); (2)Sorbitol group (5.6 mmol/L glucose + 19.4 mmol/L sorbitol); (3) High glucose group (25 mmol/L glucose); (4) Losartan group (25 mmol/L glucose + 10(5) mol/L losartan); (5) ERK inhibitors group (25 mmol/L glucose + 25 micromol/L PD98059). After 48 hours, the phosphorylation of ERK1/2 were detected by Western blot. After 72 hours, the protein and mRNA expression level of CTGF were assessed by Western blot and real-time PCR.


RESULTS
High glucose induced the phosphorylation of ERK1/2 in a time-dependent manner. The protein expression of phosphor-ERK1/2 and CTGF were increased in high glucose group comparing with low glucose group(P<0.01), and reduced in losartan group and ERK inhibitors group comparing with high glucose group(P<0.05). The mRNA expression of CTGF was increased in high glucose group comparing with low glucose group(P<0.01) , and reduced in losartan group and ERK inhibitors group comparing with high glucose group(P<0.01).


CONCLUSIONS
Losartan can inhibit high glucose-induced CTGF expression in mouse mesangial cells, and the mechanisms maybe involve the interruption of ERK1/2 MAPK pathway.
Wang
Ling
L
Department of Nephrology, Xiangya Hospital, Central South University, Changsha 410008, China.
Tao
Li-jian
LJ
Peng
Zhang-zhe
ZZ
Ning
Wang-bin
WB
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D019808:Losartan / Q000494:pharmacology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
D047228:Angiotensin II Type 1 Receptor Blockers; C526318:CCN2 protein, mouse; D055513:Connective Tissue Growth Factor; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D005947:Glucose; D019808:Losartan