Augmenter of liver regeneration ameliorates renal fibrosis in rats with obstructive nephropathy.
Renal fibrosis is a hallmark in CKD (chronic kidney disease) and is strongly correlated to the deterioration of renal function that is characterized by tubulointerstitial fibrosis, tubular atrophy, glomerulosclerosis and disruption of the normal architecture of the kidney. ALR (augmenter of liver regeneration) is a growth factor with biological functions similar to those of HGF (hepatocyte growth factor). In this study, our results indicate that endogenous ALR is involved in the pathological progression of renal fibrosis in UUO (unilateral ureteral obstruction) rat model. Moreover, we find that administration of rhALR (recombinant human ALR) significantly alleviates renal interstitial fibrosis and reduces renal-fibrosis-related proteins in UUO rats. Further investigation reveals that rhALR suppresses the up-regulated expression of TGF-β1 (transforming growth factor β1) induced by UUO operation in the obstructed kidney, and inhibits Smad2 and Smad3 phosphorylation activated by the UUO-induced injury in the animal model. Therefore we suggest that ALR is involved in the progression of renal fibrosis and administration of rhALR protects the kidney against renal fibrosis by inhibition of TGF-β/Smad activity.
*Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
Guo-Tao
GT
Chen
*Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
Ling
L
Zhang
*Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
Xiao-Hui
XH
Liao
*Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
Ru-Yu
RY
Yan
*Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
Ying
Y
Li
†Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
Hang
H
Sun
†Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
Hui
H
Guo
†Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
Qi
Q
Liu
D000818:Animals; D003579:Cytochrome Reductases / Q000494:pharmacology*; D004195:Disease Models, Animal; D005355:Fibrosis; D006801:Humans; D008297:Male; D050862:Oxidoreductases Acting on Sulfur Group Donors; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D014517:Ureteral Obstruction / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D003579:Cytochrome Reductases; C500897:GFER protein, human; D050862:Oxidoreductases Acting on Sulfur Group Donors