Tranilast inhibits cell proliferation, migration and invasion of human hypertrophic scar fibroblasts by NOP2-mediated m5C methylation on COL1A1.

Hypertrophic scar (HS), a fibroplastic skin disorder, results from excessive extracellular matrix production. The m5C modification influences disease progression by regulating RNA stability, yet its role in HS is still unknown. This study aims to to investigate m5C's role in HS and tranilast's mechanism in modulating HSFB functions. Cell function was assessed using CCK-8, EdU, flow cytometry and transwell assays to detect viability, proliferation, apoptosis, migration and invasion. m5C levels and m5C regulator expression were analyzed by dot blot and qPCR. Mechanism were investigated by methylated RNA immunoprecipitation (MeRIP), RIP and dual luciferase report. Tranilast dose-dependently suppressed HSFB viability, proliferation, migration and invasion while promoting apoptosis, with 300 μM showing maximal effects. It reduced m5C levels and NOP2 expression, with direct NOP2 interaction. NOP2 overexpression counteracted tranilast's inhibitory effects and stabilized COL1A1 mRNA via m5C modification. COL1A1 knockdown reversed the NOP2-mediated restoration of HSFB malignant phenotypes in tranilast-treated cells. Tranilast downregulates NOP2 to inhibit m5C modification of COL1A1, thereby suppressing COL1A1 expression and impairing HSFB proliferation, invasion, and migration. This study may provide a novel theoretical basis the mechanism of tranilast regulation of HS.