title: Augmenter of liver regeneration inhibits TGF-β1-induced renal tubular epithelial-to-mesenchymal transition via suppressing TβR II expression in vitro.
abstract: 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-β1 (TGF-β1) signaling pathway. Further investigation revealed that rhALR suppresses the expression of TGF-β receptor type II (TβR II) and significantly alleviates TGF-β1-induced phosphorylation of Smad2 and nuclear factor-κB (NF-κB). 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.
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Liao
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China. Electronic address: lindazhang8508@hotmail.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
authors.forename: Guo-Tao
authors.initials: GT
authors.lastname: Chen
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
authors.forename: Ru-Yu
authors.initials: RY
authors.lastname: Yan
authors.affiliation: Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Sun
authors.affiliation: Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.affiliation: Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China. Electronic address: txzzliuqi@163.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D058750:Epithelial-Mesenchymal Transition; D005455:Fluorescent Antibody Technique; D006801:Humans; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D050862:Oxidoreductases Acting on Sulfur Group Donors
chemical_list: D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D012333:RNA, Messenger; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D051899:Smad2 Protein; D053773:Transforming Growth Factor beta1; C497782:SMAD2 protein, human; C088825:GFER protein, rat; D050862:Oxidoreductases Acting on Sulfur Group Donors
keywords: Augmenter of liver regeneration; Renal tubular epithelial cells; TGFβR II; Transforming growth factor-β1; Tubular epithelial-to-mesenchymal transition