AMPKα2 reduces renal epithelial transdifferentiation and inflammation after injury through interaction with CK2β

Shulan Qiu; Zhicheng Xiao; Chunmei Piao; Jing Zhang; Yanjun Dong; Wei Cui; Xin Liu; Youyi Zhang; Jie Du

doi:10.1002/path.4579

AMPKα2 reduces renal epithelial transdifferentiation and inflammation after injury through interaction with CK2β

J Pathol. 2015 Nov;237(3):330-42. doi: 10.1002/path.4579. Epub 2015 Jul 23.

Authors

Shulan Qiu^{1

2

3}, Zhicheng Xiao^{1

2

3}, Chunmei Piao^{1

2

3}, Jing Zhang^{1

2

3}, Yanjun Dong^{1

2

3}, Wei Cui^{1

2

3}, Xin Liu⁴, Youyi Zhang⁵, Jie Du^{1

2

3}

Affiliations

¹ Beijing AnZhen Hospital, Capital Medical University, Beijing, People's Republic of China.
² Key Laboratory of Remodeling-related Cardiovascular Diseases, Ministry of Education, Beijing, People's Republic of China.
³ Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, People's Republic of China.
⁴ Centre for Molecular Systems Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, People's Republic of China.
⁵ Laboratory of Cardiovascular Bioactive Molecules, School of Basic Medical Sciences, Peking University Health Science Centre, Beijing, People's Republic of China.

PMID: 26108355
DOI: 10.1002/path.4579

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.

Keywords: AMPKα2; CK2β; EMT; fibrosis; renal inflammation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

AMP-Activated Protein Kinases / deficiency
AMP-Activated Protein Kinases / genetics
AMP-Activated Protein Kinases / metabolism*
Animals
Casein Kinase II / genetics
Casein Kinase II / metabolism*
Cell Line
Cell Transdifferentiation*
Chemokine CCL2 / metabolism
Chemokine CXCL1 / metabolism
Disease Models, Animal
Enzyme Activation
Epithelial Cells / enzymology*
Epithelial Cells / immunology
Epithelial Cells / pathology
Epithelial-Mesenchymal Transition*
Fibrosis
Humans
Inflammation Mediators / metabolism
Kidney Tubules, Proximal / enzymology*
Kidney Tubules, Proximal / immunology
Kidney Tubules, Proximal / pathology
Mice, Inbred C57BL
Mice, Knockout
Nephritis, Interstitial / enzymology
Nephritis, Interstitial / genetics
Nephritis, Interstitial / immunology
Nephritis, Interstitial / pathology
Nephritis, Interstitial / prevention & control*
Protein Binding
RNA Interference
Smad3 Protein / metabolism
Transfection
Ureteral Obstruction / complications
Wnt Signaling Pathway
beta Catenin / metabolism

Substances

CTNNB1 protein, mouse
Ccl2 protein, mouse
Chemokine CCL2
Chemokine CXCL1
Cxcl1 protein, mouse
Inflammation Mediators
Smad3 Protein
Smad3 protein, mouse
beta Catenin
AMPK alpha2 subunit, mouse
Casein Kinase II
PRKAA2 protein, human
AMP-Activated Protein Kinases