Involvement of notch signaling in wound healing.
The Notch signaling pathway is critically involved in cell fate decisions during development of many tissues and organs. In the present study we employed in vivo and cell culture models to elucidate the role of Notch signaling in wound healing. The healing of full-thickness dermal wounds was significantly delayed in Notch antisense transgenic mice and in normal mice treated with gamma-secretase inhibitors that block proteolytic cleavage and activation of Notch. In contrast, mice treated with a Notch ligand Jagged peptide showed significantly enhanced wound healing compared to controls. Activation or inhibition of Notch signaling altered the behaviors of cultured vascular endothelial cells, keratinocytes and fibroblasts in a scratch wound healing model in ways consistent with roles for Notch signaling in wound healing functions all three cell types. These results suggest that Notch signaling plays important roles in wound healing and tissue repair, and that targeting the Notch pathway might provide a novel strategy for treatment of wounds and for modulation of angiogenesis in other pathological conditions.
Chigurupati
Srinivasulu
S
Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland, United States of America.
Arumugam
Thiruma V
TV
Son
Tae Gen
TG
Lathia
Justin D
JD
Jameel
Shafaq
S
Mughal
Mohamed R
MR
Tang
Sung-Chun
SC
Jo
Dong-Gyu
DG
Camandola
Simonetta
S
Giunta
Marialuisa
M
Rakova
Irina
I
McDonnell
Nazli
N
Miele
Lucio
L
Mattson
Mark P
MP
Poosala
Suresh
S
D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors; D000818:Animals; D002135:Calcium-Binding Proteins / Q000008:administration & dosage; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000008:administration & dosage; D051379:Mice; D008822:Mice, Transgenic; D051880:Receptors, Notch / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D014945:Wound Healing
D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D053829:Amyloid Precursor Protein Secretases