Recombinant human endostatin reduces hypertrophic scar formation in rabbit ear model through down-regulation of VEGF and TIMP-1.
BACKGROUND
Recombinant human endostatin (Endostar) has been widely used to suppress angiogenesis in carcinoma patients. Hypertrophic scar (HS) tissue, much like a carcinoma, is often associated with angiogenesis. However, there have been few studies conducted on the effects of Endostar on HS or its mechanism.


OBJECTIVE
This paper investigated the effects Endostar on the HS of rabbit ears and studied the effects of Endostar on VEGF and TIMP-1 expression.


METHODS
Sixteen New Zealand white rabbits were used to establish HS models. Then, rabbit ears containing HS were randomly assigned to either the Endostar group or the control group. The changes of appearance and histology were evaluated using the naked eye, hematoxylin eosin staining, and a scar elevation index. The VEGF and TIMP-1 expressions were detected by immunohistochemical staining, RT-PCR, and western blot.


RESULTS
The thickness of the connective tissue in the Endostar group were thinner, the numbers of micro vessels and fibroblasts were fewer, and the collagen fibers were smoother. Moreover, the mRNA and protein expressions of VEGF and TIMP-1 in the Endostar group were significantly lower than those in the control group.


CONCLUSIONS
The results suggested that Endostar reduced the formation of HS by down-regulation of VEGF and TIMP-1 expressions.
Department of Orthopedics, First Affiliated Hospital of Chongqing Medical University, Chongqing, China; wangpeng.2015@hotmail.com.
Peng
P
Wang
Department of Otolaryngology, First Affiliated Hospital of Chongqing Medical University, Chongqing, China; pearl1984@sina.com.
Li-Zhu
LZ
Jiang
Department of Burn and Plastic Surgery, First Affiliated Hospital of Chongqing Medical University, Chongqing, China; CQXuebin@126.com.
Bin
B
Xue
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001707:Biopsy, Needle; D017439:Cicatrix, Hypertrophic / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation; D004431:Ear, External / Q000187:drug effects; D043169:Endostatins / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008297:Male; D011817:Rabbits; D011897:Random Allocation; D019714:Tissue Inhibitor of Metalloproteinases / Q000187:drug effects*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects*
D020533:Angiogenesis Inhibitors; D043169:Endostatins; D019714:Tissue Inhibitor of Metalloproteinases; D042461:Vascular Endothelial Growth Factor A
Endostar; endostatin; hypertrophic scar; tissue inhibitor of metalloproteinase-1; vascular endothelial growth factor