Pathological scars, including hypertrophic scars and keloids, are abnormal outcomes of the skin wound healing process, characterized by aberrant fibroblast activity and excessive accumulation of extracellular matrix (ECM). Current treatment options such as silicone gel sheeting, intralesional corticosteroid injection, surgical excision, radiotherapy, and laser therapy are nonspecific and show a high recurrence rate. Our previous study clarified that the expression of CEBPA was significantly downregulated in keloids and CEBPA negatively regulates ECM components’ deposition showing the antifibrotic therapeutic potential of it. Additionally, the first in‐human small activating RNA (saRNA) drug, CEBPA‐saRNA, has been proved effective in reversing cirrhosis and fibrosis in liver cancer and is currently undergoing a clinical trial. In this study, we found that CEBPA is downregulated in both hypertrophic scar and keloid tissue and fibroblasts compared to normal skin. Therapeutically, CEBPA‐saRNA successfully activated the expression of CEBPA both in vitro and in vivo and decreased the expression of ECM components, including collagen Type I (COL1), collagen Type III (COL3), and fibronectin 1 (FN1), demonstrating significant antifibrotic effects. Overall, this preclinical study demonstrated the therapeutic potential of CEBPA‐saRNA in reducing pathological scar formation by targeting excessive ECM component deposition, offering a promising and specific treatment approach for skin fibrotic diseases.
Gu et al. (Thu,) studied this question.