Gypenosides inhibit renal fibrosis by regulating expression of related genes in rats with unilateral ureteral obstruction.
BACKGROUND
Transforming growth factor ß1 (TGF-ß1), connective tissue growth factor (CTGF) and Smad7 are potent components of fibrogenesis-related signal transduction pathways. Renal fibrosis is the major pathological change in the rat models with unilateral ureteral obstruction (UUO). Investigating the effects of gypenosides (GPs) on the expression of fibrogenesis-related genes in the UUO model may lead to the development of effective therapy for renal diseases.


METHODS
Rats were randomly divided into 3 experimental groups: (i) sham operation rats treated with saline (sham group), (ii) UUO model rats treated with saline (control group) and (iii) UUO model rats treated with GPs (GPs group). Blood urea nitrogen and serum creatinine were detected as the measurement of renal function. UUO-treated kidney tissues were taken for assessment of renal damage index and determination of related gene expression through immunohistochemistry and RT-PCR.


RESULTS
UUO-induced tubulointerstitial damage and fibrosis were attenuated by the application of GPs (day 3 and day 7, p<0.01; day 14, p<0.05). The expression of TGF-ß1 and CTGF was significantly reduced with GPs treatment (TGF-ß1, p<0.01; CTGF, p<0.05). Smad7 expression was elevated with GPs treatment at days 7 and 14 (p<0.01). GPs' protective effects on renal function were also demonstrated with this UUO model.


CONCLUSIONS
These results suggest that UUO-induced tubulointerstitial fibrosis can be effectively attenuated by GPs application. GPs-mediated down-regulation of TGF-ß1 and CTGF and up-regulation of Smad7 are essential for their effects of antifibrogenesis.
Zhang
Yong
Y
Division of Nephrology, The Affiliated Taihe Hospital, Yunyang Medical College, Shiyan, Hubei, PR China. zhangyong968@gmail.com
Zhang
Jian-E
JE
Xiao
Hou-Qin
HQ
Wu
Ping-Yong
PY
Bai
Shou-Jun
SJ
D000199:Actins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001806:Blood Urea Nitrogen; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D005786:Gene Expression Regulation; D029774:Gynostemma; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014517:Ureteral Obstruction / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
D000199:Actins; D015415:Biomarkers; D055513:Connective Tissue Growth Factor; D003404:Creatinine; D010936:Plant Extracts; D012333:RNA, Messenger; D051906:Smad7 Protein; D053773:Transforming Growth Factor beta1; C526316:CCN2 protein, rat; C497808:Smad7 protein, rat; C508962:Tgfb1 protein, rat; C474918:gypenoside; C498862:Acta2 protein, rat