Augmenter of liver regeneration inhibits TGF-beta 1-induced renal tubular epithelial-to-mesenchymal transition via suppressing T beta R II expression in vitro

作者：Liao Xiao hui; Zhang Ling^*; Chen Guo tao; Yan Ru yu; Sun Hang; Guo Hui; Liu Qi

来源：Experimental Cell Research, 2014, 327(2): 287-296.

DOI：10.1016/j.yexcr.2014.07.001

• Augmenter of liver regeneration
• Tubular epithelial-to-mesenchymal transition
• Renal tubular epithelial cells
• Transforming growth factor-beta 1
• TGF beta R II

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.

• 出版日期2014-10-1
• 单位重庆医科大学