Augmenter of liver regeneration inhibits TGF-[beta]1-induced renal tubular epithelial-to-mesenchymal transition via suppressing T[beta]R II expression in vitro.
Liao, Xiao-hui a; Zhang, Ling a,*; Chen, Guo-tao a; Yan, Ru-yu a; Sun, Hang b; Guo, Hui b; Liu, Qi b,**
[Article]
Experimental Cell Research.
327(2):287-296, October 2014.
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: Tubular epithelial-to-mesenchymal transition (EMT) plays a crucial role in the progression of renal tubular interstitial fibrosis (TIF), which subsequently leads to chronic kidney disease (CKD) and eventually, end-stage renal disease (ESRD). We propose that augmenter of liver regeneration (ALR), a member of the newly discovered ALR/Erv1 protein family shown to ameliorate hepatic fibrosis, plays a similar protective role in renal tubular cells and has potential as a new treatment option for CKD. Here, we showed that recombinant human ALR (rhALR) inhibits EMT in renal tubular cells by antagonizing activation of the transforming growth factor-[beta]1 (TGF-[beta]1) signaling pathway. Further investigation revealed that rhALR suppresses the expression of TGF-[beta] receptor type II (T[beta]R II) and significantly alleviates TGF-[beta]1-induced phosphorylation of Smad2 and nuclear factor-[kappa]B (NF-[kappa]B). No apparent adverse effects were observed upon the addition of rhALR alone to cells. These findings collectively suggest that ALR plays a role in inhibiting progression of renal tubular EMT, supporting its potential utility as an effective antifibrotic strategy to reverse TIF in CKD.
* ALR is involved in the pathological progression of renal EMT in NRK-52E cells.
* ALR suppresses the expression of T[beta]RII and the phosphorylation of Smad2 and NF-[kappa]B.
* ALR plays a role in inhibiting progression of renal tubular EMT.
(C) 2014Elsevier, Inc.