TY - JOUR
T1 - Activation of Src kinase in platelet-derived growth factor-B-dependent tubular regeneration after acute ischemic renal injury
AU - Takikita-Suzuki, Mikiko
AU - Haneda, Masakazu
AU - Sasahara, Masakiyo
AU - Owada, M. Koji
AU - Nakagawa, Takahiko
AU - Isono, Motohide
AU - Takikita, Shoichi
AU - Koya, Daisuke
AU - Ogasawara, Kazumasa
AU - Kikkawa, Ryuichi
PY - 2003/7/1
Y1 - 2003/7/1
N2 - We previously reported that the platelet-derived growth factor B-chain (PDGF-B)/PDGF receptor (PDGFR) axis is involved in tubular regeneration after ischemia/reperfusion injury of the kidney. In the present study, we examined the activation of Src tyrosine kinase, a crucially important signaling molecule for PDGFR, and assessed the role of Src in PDGF-B-dependent renal tubular regeneration after ischemia/reperfusion injury. Immunoblot using clone 28, a monoclonal antibody specific for the active form of Src kinases, demonstrated increased active Src expression in the injured rat kidney 6 hours after reperfusion with peak activation at 12 hours. In vitro kinase assay confirmed increased Src activity that concurred with PDGFR-β activation as detected by the increment of receptor-phosphorylated tyrosine. Immunohistochemistry using clone 28 demonstrated that active Src was preferentially expressed in the S3 segment of the proximal tubule in reperfused kidney, where it is not normally expressed. This enhanced expression of active Src was colocalized with the increased PDGFR expression in the tubular cells that were undergoing cell proliferation cycle. Trapidil administration suppressed Src and PDGFR-β activation in the reperfused kidney and resulted in deteriorated renal function. These findings suggest that active Src participates in PDGF-B-dependent regeneration of tubular cells from acute ischemic injury.
AB - We previously reported that the platelet-derived growth factor B-chain (PDGF-B)/PDGF receptor (PDGFR) axis is involved in tubular regeneration after ischemia/reperfusion injury of the kidney. In the present study, we examined the activation of Src tyrosine kinase, a crucially important signaling molecule for PDGFR, and assessed the role of Src in PDGF-B-dependent renal tubular regeneration after ischemia/reperfusion injury. Immunoblot using clone 28, a monoclonal antibody specific for the active form of Src kinases, demonstrated increased active Src expression in the injured rat kidney 6 hours after reperfusion with peak activation at 12 hours. In vitro kinase assay confirmed increased Src activity that concurred with PDGFR-β activation as detected by the increment of receptor-phosphorylated tyrosine. Immunohistochemistry using clone 28 demonstrated that active Src was preferentially expressed in the S3 segment of the proximal tubule in reperfused kidney, where it is not normally expressed. This enhanced expression of active Src was colocalized with the increased PDGFR expression in the tubular cells that were undergoing cell proliferation cycle. Trapidil administration suppressed Src and PDGFR-β activation in the reperfused kidney and resulted in deteriorated renal function. These findings suggest that active Src participates in PDGF-B-dependent regeneration of tubular cells from acute ischemic injury.
UR - http://www.scopus.com/inward/record.url?scp=0037631389&partnerID=8YFLogxK
U2 - 10.1016/S0002-9440(10)63651-6
DO - 10.1016/S0002-9440(10)63651-6
M3 - 学術論文
C2 - 12819032
AN - SCOPUS:0037631389
SN - 0002-9440
VL - 163
SP - 277
EP - 286
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 1
ER -