CLC number: R644
On-line Access: 2024-08-27
Received: 2023-10-17
Revision Accepted: 2024-05-08
Crosschecked: 2013-01-03
Cited: 14
Clicked: 5677
Hai-tao Ren, Hang Hu, Yuan Li, Hong-fei Jiang, Xin-lei Hu, Chun-mao Han. Endostatin inhibits hypertrophic scarring in a rabbit ear model[J]. Journal of Zhejiang University Science B, 2013, 14(3): 224-230.
@article{title="Endostatin inhibits hypertrophic scarring in a rabbit ear model",
author="Hai-tao Ren, Hang Hu, Yuan Li, Hong-fei Jiang, Xin-lei Hu, Chun-mao Han",
journal="Journal of Zhejiang University Science B",
volume="14",
number="3",
pages="224-230",
year="2013",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1200077"
}
%0 Journal Article
%T Endostatin inhibits hypertrophic scarring in a rabbit ear model
%A Hai-tao Ren
%A Hang Hu
%A Yuan Li
%A Hong-fei Jiang
%A Xin-lei Hu
%A Chun-mao Han
%J Journal of Zhejiang University SCIENCE B
%V 14
%N 3
%P 224-230
%@ 1673-1581
%D 2013
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1200077
TY - JOUR
T1 - Endostatin inhibits hypertrophic scarring in a rabbit ear model
A1 - Hai-tao Ren
A1 - Hang Hu
A1 - Yuan Li
A1 - Hong-fei Jiang
A1 - Xin-lei Hu
A1 - Chun-mao Han
J0 - Journal of Zhejiang University Science B
VL - 14
IS - 3
SP - 224
EP - 230
%@ 1673-1581
Y1 - 2013
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1200077
Abstract: Objective: The present study was designed to use an in vivo rabbit ear scar model to investigate the efficacy of systemic administration of endostatin in inhibiting scar formation. Methods: Eight male New Zealand white rabbits were randomly assigned to two groups. Scar model was established by making six full skin defect wounds in each ear. For the intervention group, intraperitoneal injection of endostatin was performed each day after the wound healed (about 15 d post wounding). For the control group, equal volume of saline was injected. Thickness of scars in each group was measured by sliding caliper and the scar microcirculatory perfusion was assessed by laser Doppler flowmetry on Days 15, 21, 28, and 35 post wounding. Rabbits were euthanatized and their scars were harvested for histological and proteomic analyses on Day 35 post wounding. Results: Macroscopically, scars of the control group were thicker than those of the intervention group. Significant differences between the two groups were observed on Days 21 and 35 (p<0.05). Scar thickness, measured by scar elevation index (SEI) at Day 35 post wounding, was significantly reduced in the intervention group (1.09±0.19) compared with the controls (1.36±0.28). Microvessel density (MVD) observed in the intervention group (1.73±0.94) was significantly lower than that of the control group (5.63±1.78) on Day 35. The distribution of collagen fibers in scars treated with endostatin was relatively regular, while collagen fibers in untreated controls were thicker and showed disordered alignment. Western blot analysis showed that the expressions of type I collagen and Bcl-2 were depressed by injection of endostatin. Conclusions: Our results from the rabbit ear hypertrophic scar model indicate that systemic application of endostatin could inhibit local hypertrophic scar formation, possibly through reducing scar vascularization and angiogenesis. Our results indicated that endostatin may promote the apoptosis of endothelial cells and block their release of platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF), thereby controlling collagen production by fibroblasts. Blood vessel-targeted treatment may be a promising strategy for scar therapy.
[1]Amadeu, T., Braune, A., Mandarim-de-Lacerda, C., Porto, L.C., Desmouliere, A., Costa, A., 2003. Vascularization pattern in hypertrophic scars and keloids: a stereological analysis. Pathol. Res. Pract., 199(7):469-473.
[2]Bao, P., Kodra, A., Tomic-Canic, M., Golinko, M.S., Ehrlich, H.P., Brem, H., 2009. The role of vascular endothelial growth factor in wound healing. J. Surg. Res., 153(2):347-358.
[3]Camus, J.P., Koeger, A.C., 1986. d-penicillamine and collagen. Ann. Biol. Clin. (Paris), 44(3):296-299.
[4]Ehrlich, H.P., Kelley, S.F., 1992. Hypertrophic scar: an interruption in the remodeling of repair—a laser doppler blood flow study. Plast. Reconstr. Surg., 90(6):993-998.
[5]Fan, T.J., Han, L.H., Cong, R.S., Liang, J., 2005. Caspase family proteases and apoptosis. Acta Biochim. Biophys. Sin., 37(11):719-727.
[6]Kim, Y.S., Jung, D.H., Kim, N.H., Lee, Y.M., Jang, D.S., Song, G.Y., Kim, J.S., 2007. KIOM-79 inhibits high glucose or AGEs-induced VEGF expression in human retinal pigment epithelial cells. J. Ethnopharmacol., 112(1):166-172.
[7]Kim, Y.S., Kim, J., Kim, C.S., Sohn, E.J., Lee, Y.M., Jeong, I.H., Kim, H., Jang, D.S., Kim, J.S., 2011. KIOM-79, an inhibitor of AGEs-protein cross-linking, prevents progression of nephropathy in zucker diabetic fatty rats. Evid. Based Compl. Altern. Med., 2011:761859.
[8]Kirsner, R.S., Eaglstein, W.H., 1993. The wound healing process. Dermatol. Clin., 11(4):629-640.
[9]Kischer, C.W., 1992. The microvessels in hypertrophic scars, keloids and related lesions: a review. J. Submicrosc. Cytol. Pathol., 24(2):281-296.
[10]Leventhal, D., Furr, M., Reiter, D., 2006. Treatment of keloids and hypertrophic scars: a meta-analysis and review of the literature. Arch. Fac. Plast. Surg., 8(6):362-368.
[11]Marcus, J.R., Tyrone, J.W., Bonomo, S., Xia, Y., Mustoe, T.A., 2000. Cellular mechanisms for diminished scarring with aging. Plast. Reconstr. Surg., 105(5):1591-1599.
[12]Mazars, A., Geneste, O., Hickman, J., 2005. The bcl-2 family of proteins as drug targets. J. Soc. Biol., 199(3):253 (in French).
[13]Miller, D.K., 1997. The role of the caspase family of cysteine proteases in apoptosis. Semin. Immunol., 9(1):35-49.
[14]Morris, D., Wu, L., Zhao, L., Bolton, L., Roth, S., Ladin, D., Mustoe, T., 1997. Acute and chronic animal models for excessive dermal scarring: quantitative studies. Plast. Reconstr. Surg., 100(3):674.
[15]O'Reilly, M.S., Boehm, T., Shing, Y., Fukai, N., Vasios, G., Lane, W.S., Flynn, E., Birkhead, J.R., Olsen, B.R., Folkman, J., 1997. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell, 88(2):277-285.
[16]Portt, L., Norman, G., Clapp, C., Greenwood, M., Greenwood, M.T., 2011. Anti-apoptosis and cell survival: a review. Biochim. Biophys. Acta, 1813(1):238-259.
[17]Rosca, E.V., Koskimaki, J.E., Rivera, C.G., Pandey, N.B., Tamiz, A.P., Popel, A.S., 2011. Anti-angiogenic peptides for cancer therapeutics. Curr. Pharm. Biotechnol., 12(8):1101-1016.
[18]Saulis, A.S., Mogford, J.H., Mustoe, T.A., 2002a. Effect of mederma on hypertrophic scarring in the rabbit ear model. Plast. Reconstr. Surg., 110(1):177-183, discussion 184-186.
[19]Saulis, A.S., Chao, J.D., Telser, A., Mogford, J.E., Mustoe, T.A., 2002b. Silicone occlusive treatment of hypertrophic scar in the rabbit model. Aesthet. Surg. J., 22(2):147-153.
[20]Song, B., Lu, K., Zhang, Y., Guo, S., Han, Y., Ma, F., Li, H., 2008a. Angiogenesis in hypertrophic scar of rabbit ears and effect of extracellular protein with metalloprotease and thrombospondin 1 domains on hypertrophic scar. Chin. J. Repar. Reconstr. Surg., 22(1):70-74.
[21]Song, B.Q., Lu, K.H., Guo, S.Z., Zhang, Y., Peng, P., Ma, F.C., Li, H.Y., 2008b. Effect of METH1 gene transfection on the proliferation of rabbit’s ear scar. Chin. J. Plast. Surg., 24(2):148-150 (in Chinese).
[22]Song, B., Zhang, W., Guo, S., Han, Y., Zhang, Y., Ma, F., Zhang, L., Lu, K., 2009. Adenovirus-mediated METH1 gene expression inhibits hypertrophic scarring in a rabbit ear model. Wound Repair Regen., 17(4):559-568.
[23]Tandara, A.A., Mustoe, T.A., 2008. The role of the epidermis in the control of scarring: evidence for mechanism of action for silicone gel. J. Plast. Reconstr. Aesthet. Surg., 61(10):1219-1225.
[24]Thomas, D.W., Hopkinson, I., Harding, K.G., Shepherd, J.P., 1994. The pathogenesis of hypertrophic/keloid scarring. Int. J. Oral Maxillof. Surg., 23(4):232-236.
[25]Wang, Z.Y., Fei, S., Lianju, X., Yingkai, L., Chun, Q., Shuliang, L., Xiqiao, W., 2012. Endostar injection inhibits rabbit ear hypertrophic scar formation. Int. J. Low Extrem. Wounds, 11(4):271-276.
[26]Zheng, M.J., 2009. Endostatin derivative angiogenesis inhibitors. Chin. Med. J. (Engl.), 122(16):1947-1951.
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