[Blocking of Notch signaling decreased scar formation in rabbit ear hypertrophic scar model].
OBJECTIVE
To investigate the effects of Notch signaling on scars in a rabbit ear model of hypertrophic scarring.


METHODS
The hypertrophic scar of rabbits' ears was reproduced. The left rabbit's ear wounds as the N-[N-(3,5-difluorophenacetyl-L-alanyl)]-(S)-phenylglycine t-butyl ester (DAPT) treated group were treated intradermally with the gamma-secretase inhibitor DAPT to inhibit the activation of Notch at 1, 3, 7 and 14 day time points. The right ears as the control group were treated with normal saline at the same time points. Experimental and control wounds were harvested on days 14, 21, 28 and 35 post wounding, and then examined histologically to quantify hypertrophic index and fibroblasts. The expression of epidermal differentiation markers-keratin 14 (K14), keratin 19 (K19), Involucrin and Notch downstream molecules-P21, P63 were examined and analyzed with immunohistochemistry staining.


RESULTS
Both hypertrophic index (1.93 +/- 0.32, 1.82 +/- 0.36, 1.79 +/- 0.25) and number of fibroblasts [(4.08 +/- 0.88), (3.30 +/- 0.53), (3.19 +/- 0.73) x 10(3)/mm(2)] in the DAPT treated group were significantly reduced on days 21, 28 and 35, compared with the control group [2.56 +/- 0.29, 2.61 +/- 0.30, 2.58 +/- 0.39, and (5.45 +/- 0.99), (4.80 +/- 1.13), (4.43 +/- 1.17) x 10(3)/mm(2), all P < 0.01)]. The K19, K14 and P63 increased their expression in the DAPT treated group (28.6% +/- 5.7%, 53.1% +/- 4.5%, 57.0% +/- 5.8%) relative to the control group (10.1% +/- 2.8%, 30.8% +/- 4.9%, 16.5% +/- 2.2%, all P < 0.01) on day 14 post wounding, while the Involucrin and P21 decreased their expression in the DAPT treated group (12.3% +/- 1.9%, 11.0% +/- 1.7%) relative to the control group (29.3% +/- 4.6%, 44.3% +/- 3.5%, both P < 0.01).


CONCLUSIONS
Inactivation of Notch signaling will inhibit scar epidermis to over-differentiation, and thereby inhibit proliferation of hypertrophic scars in the rabbit ears.
Diao
Jian-Sheng
JS
Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Zhang
Xi
X
Ren
Jing
J
Zeng
Hai-Feng
HF
Liu
Bei
B
Ma
Fu-Cheng
FC
Wang
Ying-Mei
YM
Yang
Xiao-Ting
XT
Guo
Shu-Zhong
SZ
Xia
Wei
W
D000818:Animals; D002454:Cell Differentiation; D017439:Cicatrix, Hypertrophic / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D011817:Rabbits; D051880:Receptors, Notch / Q000378:metabolism*
D051880:Receptors, Notch