The activation of extracellular signal-regulated kinase is responsible for podocyte injury

Podocyte and its slit diaphragm play an important role in maintaining normal glomerular filtration barrier function and structure. Podocyte apoptosis and slit diaphragm injury leads to proteinuria and glomerulosclerosis. However, the molecular mechanism of podocyte injury remains poorly understood. The family of mitogen-activated protein kinases including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase, and p38 signal pathways, are implicated in the progression of various glomerulopathies. However, the role of the activated signal pathway(s) in podocyte injury is elusive. This study examined phosphorylation of ERK in rat puromycin aminonucleoside (PAN) nephropathy as well as conditionally immortalized mouse podocyte treated with PAN in vitro. The effect of treatment with U0126, an inhibitor of ERK, was also investigated. In PAN nephropathy, the phosphorylation of ERK was marked. In podocyte injury, the marked and sustained activation of ERK pathway was also observed before the appearance of significant podocyte apoptosis. Pretreatment with U0126 to podocyte completely inhibited ERK activation, with complete suppression podocyte apoptosis and ameliorated nephrin protein expression along with the phosphorylation of nephrin in podocyte injury. In cultured podocyte, PAN induced actin recorganition, and U0126 inhibited such change. However, U0126 did not recovery the phosphorylation change of neph1 in podocyte injury. We concluded that the sustained activation of ERK along with the phosphorylation of neph1 might be necessary for podocyte injury. The study here suggested that ERK might become a potential target for therapeutic intervention to prevent podocytes from injury which will result in proteinuria.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000279308400045&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Biochemistry & Molecular BiologySCI(E)PubMed9ARTICLE52477-24843