lncRNA COL1A2-AS1 (COL1A2 antisense RNA 1), a lncRNA overexpressed in hypertrophic scar, has been demonstrated to be involved in the hypertrophic scar formation. However, the mechanisms of lncRNA COL1A2-AS1 inhibiting the scar fibroblasts proliferation remains not well understood. In this study, we demonstrated that lncRNA COL1A2-AS1 was upregulated in hypertrophic scar tissue and fibroblasts, and suppressed fibroblasts proliferation by promoting Smad7 expression. Furthermore, we found that miR-21 was involved in lncRNA COL1A2-AS1-induced expression of Smad7, by which COL1A2-AS1 acted as endogenous sponge to adsorb miR-21 and in turn regulated Smad7 and a cascade of molecular to play a protective role in hypertrophic scar. In addition, overexpression of miR-21 attenuated COL1A2-AS1-mediated proliferation suppression of hypertrophic scar fibroblasts. In conclusion, our study demonstrated that COL1A2-AS1/miR-21/Smad pathway plays an important role in inhibiting hypertrophic scar formation, and suggested this novel pathway may be a new target for hypertrophic scar treatment. (C) 2017 Elsevier Inc. All rights reserved.