AST-120 ameliorates epithelial-to-mesenchymal transition and interstitial fibrosis in the kidneys of chronic kidney disease rats.
OBJECTIVE
Indoxyl sulfate (IS), a uremic toxin, is a risk factor for progression of chronic kidney disease (CKD). AST-120 reduces serum IS and delays the progression of CKD. This study aimed to examine whether AST-120 inhibits epithelial-to-mesenchymal transition (EMT) in the kidneys of CKD rats.


METHODS
CKD rats were produced by 5/6 nephrectomy and were divided into 2 groups: (1) CKD rats and (2) AST-120-treated CKD rats at a dosage of 4 g/kg body weight/day. After 10 weeks, their kidneys were excised for histological and immunohistochemical analysis. EMT was evaluated by immunohistochemistry of zonula occludens (ZO-1), an epithelial marker, and alpha-smooth muscle actin (α-SMA), a mesenchymal marker. Interstitial fibrosis was evaluated by Masson's trichrome staining.


RESULTS
CKD rats showed reduced expression of ZO-1 and enhanced expression of α-SMA as compared with normal rats. Administration of AST-120 to CKD rats increased expression of ZO-1 and decreased expression of α-SMA as compared with CKD rats. Further, CKD rats showed enhanced extent of interstitial fibrosis as compared with normal rats, and administration of AST-120 to CKD rats ameliorated interstitial fibrosis. CKD rats showed increased serum level of IS as compared with normal rats, whereas administration of AST-120 to CKD rats decreased both serum and urine levels of IS.


CONCLUSIONS
We conclude that AST-120 ameliorated EMT and interstitial fibrosis in the kidneys of CKD rats, probably by alleviating IS overload on the kidneys.
Department of Advanced Medicine for Uremia, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Dilinaer
D
Bolati
Hidehisa
H
Shimizu
Toshimitsu
T
Niwa
D000199:Actins / Q000032:analysis; D000327:Adsorption; D000818:Animals; D002244:Carbon / Q000627:therapeutic use*; D002465:Cell Movement; D004847:Epithelial Cells / Q000737:chemistry / Q000473:pathology* / Q000502:physiology; D005355:Fibrosis; D007150:Immunohistochemistry; D007200:Indican / Q000037:antagonists & inhibitors; D007668:Kidney / Q000737:chemistry / Q000473:pathology* / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D010087:Oxides / Q000627:therapeutic use*; D010750:Phosphoproteins / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D062826:Zonula Occludens-1 Protein
D000199:Actins; D008565:Membrane Proteins; D010087:Oxides; D010750:Phosphoproteins; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D002244:Carbon; C040896:AST 120; D007200:Indican