Genistein attenuates advanced glycation end product-induced expression of fibronectin and connective tissue growth factor.
OBJECTIVE
To investigate the effect of advanced glycation end products (AGEs) on the expression of connective tissue growth factor (CTGF) and fibronectin (FN) in human peritoneal mesothelial cells (HPMC). To observe the effect of genistein (Gen) on the expression of CTGF and FN in HPMC induced by AGEs.


METHODS
First, HPMC were stimulated with different concentrations of AGEs (0, 200, 600 and 1,000 mg/l) for 48 h; the expression of FN was detected by reverse transcription-polymerase chain reaction (RT-PCR). Second, HPMC were divided into the following groups: (1) control group, (2) AGE-treated group (600 mg/l AGEs) and (3) Gen-treated groups with 600 mg/l AGEs and 25, 50 and 100 µMGen, respectively. The expression of messenger RNA (mRNA) for FN and CTGF was measured by RT-PCR; the expression of FN and CTGF protein was detected by enzyme-linked immunosorbent assay (ELISA) after 48 h.


RESULTS
The expression of FN mRNA in HPMC increased in a dose-dependent manner after induction with AGEs. Compared with controls, 600 mg/l AGEs markedly promoted the expression of mRNA and protein for FN and CTGF. Compared with the AGE-treated group (600 mg/l), 25, 50, and 100 µM Gen significantly inhibited the expression of mRNA and protein for FN and CTGF.


CONCLUSIONS
AGEs can markedly increase the expression of mRNA and protein for FN and CTGF; however, Gen can inhibit the expression of FN and CTGF mRNA and protein stimulated by AGEs, which implies that Gen probably decreases the accumulation of extracellular matrix through inhibiting the expression of CTGF, and it may play a role in anti-peritoneal fibrosis.
Division of Renal Medicine, Guangxin Hospital, Zhejiang Chinese Medical University, Hangzhou, China. tongmengli@gmail.com
Mengli
M
Tong
Yuhui
Y
Wang
Yongjun
Y
Wang
Hongyu
H
Chen
Chengda
C
Wang
Luchun
L
Yang
Jonas
J
Axelsson
Bengt
B
Lindholm
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004848:Epithelium / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis* / Q000378:metabolism; D005786:Gene Expression Regulation; D019833:Genistein / Q000494:pharmacology*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D010537:Peritoneum / Q000166:cytology; D016133:Polymerase Chain Reaction / Q000379:methods; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
D005353:Fibronectins; D017127:Glycation End Products, Advanced; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D055513:Connective Tissue Growth Factor; D019833:Genistein