Expression and function of the Delta-1/Notch-2/Hes-1 pathway during experimental acute kidney injury.
The Notch signaling pathway consists of several receptors and their ligands Delta and Jagged and is important for embryogenesis, cellular differentiation and proliferation. Activation of Notch receptors causes their cleavage yielding cytoplastic domains that translocate into the nucleus to induce target proteins such as the basic-loop-helix proteins Hes and Hey. Here we sought to clarify the significance of the Notch signaling pathway in acute kidney injury using a rat ischemia-reperfusion injury model and cultured NRK-52E cells. Analysis of the whole kidney after injury showed increased expression of Delta-1 and Hes-1 mRNA and protein along with processed Notch-2. Confocal microscopy, using specific antibodies, showed that Delta-1, cleaved Notch-2 and Hes-1 colocalized in the same segments of the injured renal proximal tubules. Recombinant Delta-1 significantly stimulated NRK-52E cell proliferation. Our study suggests that the Delta-1/Notch-2/Hes-1 signaling pathway may regulate the regeneration and proliferation of renal tubules during acute kidney injury.
Kobayashi
T
T
Department of Nephrology and Blood Purification, Tokyo Medical and Dental University, Tokyo, Japan.
Terada
Y
Y
Kuwana
H
H
Tanaka
H
H
Okado
T
T
Kuwahara
M
M
Tohda
S
S
Sakano
S
S
Sasaki
S
S
D000208:Acute Disease; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology; D007668:Kidney / Q000098:blood supply* / Q000473:pathology / Q000502:physiology; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D051883:Receptor, Notch2 / Q000235:genetics / Q000378:metabolism*; D012038:Regeneration; D000072056:Transcription Factor HES-1; D015854:Up-Regulation
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051883:Receptor, Notch2; D000072056:Transcription Factor HES-1; C489735:Hes1 protein, rat; C497766:Notch2 protein, rat; C064045:delta protein