Treatment of keloids through Runx2 siRNA‑induced inhibition of the PI3K/AKT signaling pathway

Abstract

Keloids are a skin fibroproliferative condition characterized by the hyperproliferation of fibroblasts and the excessive deposition of extracellular matrix (ecM) compo‑ nents. Previous studies have determined that caveolin‑1 controlled hyperresponsiveness to mechanical stimuli through runt‑related transcription factor 2 (runx2) activa‑ tion in keloids. However, the molecular mechanism of runx2 regulating the pathological progression of keloids has not been elucidated. Gene ontology and Kyoto encyclopedia of Genes and Genomes (KeGG) analysis revealed that most of the differentially expressed genes (deGs), including runx2, were significantly enriched in the biological processes ‘Positive regulation of cell proliferation’, in the cellular components ‘extracellular matrix’, in the molecular func‑ tions ‘extracellular matrix structural constituents’ and in the KeGG ‘Pi3K‑akt signaling pathway’. The aim of the present study was to investigate the expression levels of the runx2 in human keloid tissues and primary human keloid fibroblasts (HKFs), and to determine the underlying molecular mechanisms involved in the fibrotic roles of Runx2 in keloid formation. runx2 expression levels were analyzed in patient keloid tissues and HKFs using western blotting, reverse transcription‑quantitative PCR (RT‑qPCR) and immunofluo‑ rescence microscopy. Primary HKFs were transfected with a small interfering rna (si) specifically targeting runx2 (si‑runx2). Subsequently, cell counting Kit‑8, wound healing and Transwell assays, flow cytometry, RT‑qPCR and western blotting were applied to evaluate the proliferation, migration.