Genistein inhibited endocytosis and fibrogenesis in transforming growth factor-β1-stimulated keloid via CTGF signaling pathways

Abstract

Background: This study aimed to evaluate soy isoflavones' effect and potential use—specifically genistein—in treating human keloid fibroblast cell lines (KFs) and in a keloid tissue culture model. Methods: to investigate the effects of genistein on keloid, a wound-healing assay was performed to detect cell migration. Flow cytometry was used to measure apoptosis. Western blotting and immunofluorescence staining were performed to detect the expression of target proteins. Keloid fibroblast tissues were isolated, cultured, and divided into the control, silenced connective tissue growth factor (CTGF) proteins, and shNC (negative control) groups. Results: genistein could suppress cell proliferation and migration and enhance apoptosis at the G2/M phase in keloid fibroblasts. Genistein inhibited the expression of collagen 1A1 I, fibronectin, and CTGF proteins, reducing collagen 1A1 accumulation. The expressions of hypoxia-inducible factor-1α (HIF-1α), transforming growth factor-β (TGF-β), and CTGF were reduced after exposure to genistein. The cell migration ability from the keloid patient’s tissues was decreased by genistein treatment and was time-dose dependent. Genistein also abated TGF-β1-induced keloid fibrosis through the endocytosis model. Additionally, genistein could increase the expression of p53 in a dose-dependent manner. Conclusions: This process may depend on the regulation of CTGF. Genistein may attenuate the activity of keloid fibroblasts and reduce keloid formation. The results of our study indicate that genistein-induced p53 undergoes apoptosis through the CTGF pathway in a P53-dependent manner, suggesting that our research provides a new strategy for developing drugs for treating keloids.