Activation of Src kinase in platelet-derived growth factor-B-dependent tubular regeneration after acute ischemic renal injury.
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 afterischemia/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-beta 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 co-localized with the increased PDGFR expression in the tubular cells that were undergoing cell proliferation cycle. Trapidil administration suppressed Src and PDGFR-beta 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.
Takikita-Suzuki
Mikiko
M
Department of Medicine, Shiga University of Medical Science, Seta, Otsu, Japan. mikitaki@belle.shiga-med.ac.jp
Haneda
Masakazu
M
Sasahara
Masakiyo
M
Owada
M Koji
MK
Nakagawa
Takahiko
T
Isono
Motohide
M
Takikita
Shoichi
S
Koya
Daisuke
D
Ogasawara
Kazumasa
K
Kikkawa
Ryuichi
R
D000818:Animals; D003404:Creatinine / Q000097:blood; D004789:Enzyme Activation; D006801:Humans; D007150:Immunohistochemistry; D007684:Kidney Tubules / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D015427:Reperfusion Injury; D014192:Trapidil / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
D010975:Platelet Aggregation Inhibitors; D018809:Proliferating Cell Nuclear Antigen; D020574:Proto-Oncogene Proteins c-sis; D003404:Creatinine; D020797:Receptor, Platelet-Derived Growth Factor beta; D019061:src-Family Kinases; D014192:Trapidil