KLF2 inhibits keloid progression by targeting PI3K/AKT-mediated MMP-2/9 signaling.

The anti-proliferation, anti-invasion, and anti-migration activities of KLF2 in keloid fibroblasts (KFs) and hypertrophic scar fibroblasts (HSFs) were investigated. KLF2 in normal skin (NF), keloid (KD), hypertrophic scar (HS) tissues, and cell lines was quantified using western blot and quantitative real-time polymerase chain reaction techniques. The processes of cell proliferation, migration, and invasion were observed in both KFs and HSFs, with pathway proteins linked to these processes pinpointed through western blot analysis. KLF2 in KD and HS tissues was lower than that in NF tissues. Enhancing KLF2 expression inhibited KF and HSF proliferation, migration, and invasion. MMP2, MMP-9, PI3K and p-Akt protein levels were inhibited in KFs with KLF2 overexpression. However, inhibition of PI3K and p-Akt protein levels was observed only in KLF2-overexpressed HSFs. In KFs with enhanced KLF2 expression, PI3K agonists eliminated the effect of KLF2 overexpression on cell migration and invasion. KLF2 inhibits the proliferation and migration of KFs by down-regulating MMP-2/9 through the PI3K/AKT pathway, suggesting that KLF2 may be a potential therapeutic target for KD. Hence, these findings offer novel perspectives on the function and molecular pathways of KLF2 in KD, as well as novel strategies for its clinical treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10616-025-00885-6.