Background
Hypertrophic scars (HSs) cause functional impairment and cosmetic deformities following operations or burns (30% to 94%). There is no target therapy yet because the pathogenesis of HS progression is not well known. In tissue fibrosis, abnormal up-regulation of zinc finger E-box binding homeobox 1 (ZEB1) is an important cause for extracellular matrix (ECM) overexpression, which is the main molecular change in HSs. The authors hypothesized that ZEB1 knockdown inhibits HS formation.
Conclusions
ZEB1 knockdown inhibits HS formation both in vitro and in vivo. However, this is an in vitro mouse model, and more validation is needed. Clinical relevance statement: The discovery of ZEB1 as a mediator of HS formation might be a potential therapeutic target in HS treatment.
Methods
ZEB1 expression in human HS and transforming growth factor-β1-induced fibroblasts were identified by polymerase chain reaction (PCR) and Western blotting. ZEB1 was knocked down by small interfering RNA in HS fibroblasts (HSFs) and the mouse HS model (C57/BL6 male mice aged 8 to 12 weeks). After 8 hours of transfection, HSFs were subjected to PCR, Western blotting, and Cell Counting Kit-8 apoptosis, migration, and contraction assays. Mouse HSs were analyzed by hematoxylin and eosin staining, PCR, and Western blotting after 56 days.
Results
ZEB1 was up-regulated in HS tissue (2.0-fold; P < 0.001). ZEB1 knockdown inhibited HSF activity (0.6-fold to 0.7-fold; P < 0.001); the expression of fibrotic markers (0.4-fold to 0.6-fold; P < 0.001); and β-catenin, cyclinD1, and c-Myc expression (0.5-fold; P < 0.001). In mouse HS models, HS skin thickness was less (1.60 ± 0.40 mm versus 4.04 ± 0.36 mm; P < 0.001) after ZEB1 knockdown. Conclusions: ZEB1 knockdown inhibits HS formation both in vitro and in vivo. However, this is an in vitro mouse model, and more validation is needed. Clinical relevance statement: The discovery of ZEB1 as a mediator of HS formation might be a potential therapeutic target in HS treatment.