title: Akt2 is involved in loss of epithelial cells and renal fibrosis following unilateral ureteral obstruction.
abstract: Obstructive nephropathy is an aggressive form of chronic kidney disease (CKD), which is characterized by an epithelial-to-mesenchymal transition (EMT) and interstitial fibrosis. However, the molecular mechanisms of EMT and fibrosis are complex and not fully understood. In this study, we investigated the contribution of Akt2 to experimental renal EMT and fibrosis using the well-established model of unilateral ureteral obstruction (UUO). We found that Akt2 and phosphor (p)-Akt protein levels were increased in the obstructed kidneys. UUO induced activation of transforming growth factor-β1 (TGF-β1) signaling. Importantly, knockout of Akt2 suppressed UUO-induced EMT, kidney fibrosis, increased GSK3β activity, and decreased expression of Snail and β-catenin. Inhibition of GSK3β with LiCl (the inhibitor of GSK3β) increased the expression of Snail and β-catenin in cultured kidney epithelial cells. Our findings suggest that Akt2 partially contributes to interstitial fibrosis following UUO and that inhibition of this signaling pathway may provide a novel approach of prevent progression of renal fibrosis.
authors.affiliation: Beijing An Zhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-related Cardiovascular Diseases, Ministry of Education, Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Aiping
authors.initials: A
authors.lastname: Lan
authors.affiliation: Beijing An Zhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-related Cardiovascular Diseases, Ministry of Education, Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Beijing An Zhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-related Cardiovascular Diseases, Ministry of Education, Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Beijing An Zhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-related Cardiovascular Diseases, Ministry of Education, Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Peng
authors.affiliation: Beijing An Zhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-related Cardiovascular Diseases, Ministry of Education, Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Yongfen
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Beijing An Zhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-related Cardiovascular Diseases, Ministry of Education, Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Du
mesh_terms: D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005355:Fibrosis; D015870:Gene Expression; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D018345:Mice, Knockout; D051057:Proto-Oncogene Proteins c-akt / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014517:Ureteral Obstruction / Q000150:complications; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D051176:beta Catenin; C494921:AKT2 protein, human; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3