CK2α promotes advanced glycation end products-induced expressions of fibronectin and intercellular adhesion molecule-1 via activating MRTF-A in glomerular mesangial cells.
Biochem Pharmacol
; 148: 41-51, 2018 02.
Article
em En
| MEDLINE
| ID: mdl-29223351
ABSTRACT
Advanced glycation end products' (AGEs) modification of extracellular matrix proteins induces crosslinking, which results in thickening of the basement membrane and activating several intracellular signaling cascades, eventually promoting the pathological progression of diabetic nephropathy (DN). We have previously confirmed that casein kinase 2α (CK2α) activates the nuclear factor of kappaB (NF-κB) signaling pathway to enhance high glucose-induced expressions of fibronectin (FN) and intercellular adhesion molecule-1 (ICAM-1) in glomerular mesangial cells (GMCs). However, to date, the mechanism by which CK2α regulates diabetic renal fibrosis is not fully understood. In view of the regulation of inflammation and fibrosis by myocardin-related transcription factor A (MRTF-A), we are highly concerned whether CK2α promotes AGEs-induced expressions of FN and ICAM-1 in glomerular mesangial cells via activation of MRTF-A, thus affecting the pathogenesis of DN. We found that CK2α and MRTF-A proteins were overexpressed in AGEs-induced diabetic kidneys. Inhibition of CK2α kinase activity or knockdown of CK2α protein expression suppressed the upregulation of FN and ICAM-1 expressions in GMCs induced by AGEs. MRTF-A knockdown compromised the expressions of FN and ICAM-1 in GMCs induced by AGEs. Moreover, inhibition of CK2α kinase activity or knockdown of CK2α protein expression restrained the protein expression and nuclear aggregation of MRTF-A. CK2α interacted with MRTF-A. Furthermore, knockdown of MRTF-A while overexpression of CK2α blocked the upregulation effect of CK2α on the protein expressions of FN and ICAM-1. These findings suggest that CK2α promotes diabetic renal fibrosis via activation of MRTF-A and upregulation of inflammatory genes.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Fibronectinas
/
Produtos Finais de Glicação Avançada
/
Molécula 1 de Adesão Intercelular
/
Caseína Quinase II
/
Células Mesangiais
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article