title: AMPKα2 reduces renal epithelial transdifferentiation and inflammation after injury through interaction with CK2β.
abstract: TGFβ1/Smad, Wnt/β-catenin and snail1 are preferentially activated in renal tubular epithelia after injury, leading to epithelial-mesenchymal transition (EMT). The stress response is coupled to EMT and kidney injury; however, the underlying mechanism of the stress response in EMT remains elusive. AMP-activated protein kinase (AMPK) signalling is responsive to stress and regulates cell energy balance and differentiation. We found that knockdown of AMPKα, especially AMPKα2, enhanced EMT by up-regulating β-catenin and Smad3 in vitro. AMPKα2 deficiency enhanced EMT and fibrosis in a murine unilateral ureteral obstruction (UUO) model. AMPKα2 deficiency also increased the expression of chemokines KC and MCP-1, along with enhanced infiltration of inflammatory cells into the kidney after UUO. CK2β interacted physically with AMPKα and enhanced AMPKα Thr172 phosphorylation and its catalytic activity. Thus, activated AMPKα signalling suppresses EMT and secretion of chemokines in renal tubular epithelia through interaction with CK2β to attenuate renal injury.
authors.affiliation: Beijing AnZhen Hospital, Capital Medical University, Beijing, People's Republic of China.|Key Laboratory of Remodeling-related Cardiovascular Diseases, Ministry of Education, Beijing, People's Republic of China.|Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, People's Republic of China.
authors.forename: Shulan
authors.initials: S
authors.lastname: Qiu
authors.affiliation: Beijing AnZhen Hospital, Capital Medical University, Beijing, People's Republic of China.|Key Laboratory of Remodeling-related Cardiovascular Diseases, Ministry of Education, Beijing, People's Republic of China.|Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, People's Republic of China.
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Beijing AnZhen Hospital, Capital Medical University, Beijing, People's Republic of China.|Key Laboratory of Remodeling-related Cardiovascular Diseases, Ministry of Education, Beijing, People's Republic of China.|Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, People's Republic of China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Piao
authors.affiliation: Beijing AnZhen Hospital, Capital Medical University, Beijing, People's Republic of China.|Key Laboratory of Remodeling-related Cardiovascular Diseases, Ministry of Education, Beijing, People's Republic of China.|Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Beijing AnZhen Hospital, Capital Medical University, Beijing, People's Republic of China.|Key Laboratory of Remodeling-related Cardiovascular Diseases, Ministry of Education, Beijing, People's Republic of China.|Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, People's Republic of China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Beijing AnZhen Hospital, Capital Medical University, Beijing, People's Republic of China.|Key Laboratory of Remodeling-related Cardiovascular Diseases, Ministry of Education, Beijing, People's Republic of China.|Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.affiliation: Centre for Molecular Systems Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Laboratory of Cardiovascular Bioactive Molecules, School of Basic Medical Sciences, Peking University Health Science Centre, Beijing, People's Republic of China.
authors.forename: Youyi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Beijing AnZhen Hospital, Capital Medical University, Beijing, People's Republic of China.|Key Laboratory of Remodeling-related Cardiovascular Diseases, Ministry of Education, Beijing, People's Republic of China.|Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Du
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D054338:Cell Transdifferentiation; D018932:Chemokine CCL2 / Q000378:metabolism; D054360:Chemokine CXCL1 / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005355:Fibrosis; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009395:Nephritis, Interstitial / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D011485:Protein Binding; D034622:RNA Interference; D051900:Smad3 Protein / Q000378:metabolism; D014162:Transfection; D014517:Ureteral Obstruction / Q000150:complications; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495267:CTNNB1 protein, mouse; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D018836:Inflammation Mediators; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D051176:beta Catenin; C534978:Prkaa2 protein, mouse; D047390:Casein Kinase II; C526181:PRKAA2 protein, human; D055372:AMP-Activated Protein Kinases
keywords: AMPKα2; CK2β; EMT; fibrosis; renal inflammation