[Effects of Hirsutella sinensis on TGF-beta1 and Snail expressions and transdifferentiation of tubular epithelial-myofibroblast in renal tissue of rats with chronic aristolochic acid nephropathy].
OBJECTIVE
To investigate the antagonizing effect of Hirsutella sinensis (HS) on renal tubular epithelial-myofibroblast transdifferentiation (TEMT) and its possible pathogenic mechanism in rats with chronic aristolochic acid nephropathy (CAAN).


METHODS
Eighteen male Sprague-Dawley rats were equally divided into 3 groups, the model (M) group, the intervention (I) group and the control (C) group. The 24 h urinary protein (UP) in rats was measured before intervention and at the end of the 1st, 4th, 8th, and 12th week, and creatinine clearance rate (CCr) was measured before intervention and at the end of the 12th week respectively. All rats were sacrificed at the end of the 12th week, their kidney was taken for examining the degree of fibrosis in renal interstitial with Masson's stain and determining mRNA and protein expressions of transforming growth factor-beta1 (TGF-beta1), Snail, alpha-smooth muscle actin (alpha-SMA) and cytokeratin in renal tissue by Real-time RT-PCR and immunohistochemistry staining, respectively.


RESULTS
Compared with the C group, CCr was significantly lower, while 24 h UP was higher; the relative area of interstitial fibrosis was significantly larger in the M group; besides, the mRNA and protein expressions of TGF-beta1, Snail and alpha-SMA were significantly up-regulated (P < 0.01 or P < 0.05), and those of cytokeratin were significantly down-regulated (P < 0.01) in renal tissue of the M group. While in the I group, all the above-mentioned abnormalities were restored to some extent (P < 0.05) and showed significant difference (all P < 0.05) as compared with those in the M group.


CONCLUSIONS
HS can downregulate TGF-beta1 and Snail expressions in renal tissue, antagonize TEMT and renal interstitial fibrosis, and improve renal function in CAAN rats.
Chai
Jing-Jing
JJ
Center of Nephrology, China-Japan Friendship Hospital, Beijing.
Chen
Yi-Pu
YP
Rui
Hong-Liang
HL
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D034341:Aristolochic Acids / Q000633:toxicity*; D054338:Cell Transdifferentiation; D002908:Chronic Disease; D032661:Cordyceps / Q000737:chemistry*; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005347:Fibroblasts / Q000187:drug effects; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism; D007684:Kidney Tubules / Q000473:pathology; D008297:Male; D008517:Phytotherapy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016211:Transforming Growth Factor alpha / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D034341:Aristolochic Acids; D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016211:Transforming Growth Factor alpha; C000604450:Snai2 protein, rat; C498862:Acta2 protein, rat; C000228:aristolochic acid I