Regulatory role of POSTN in keloid pathogenesis.

Keloids are an inflammatory cutaneous condition, which are characterized by fibroproliferative overgrowth of the skin. Although keloids are not life‑threatening, their incidence and recurrence are relatively high, thus decreasing the quality of life of patients due to pain, pruritus and cosmetic reasons. Additionally, the precise molecular mechanisms underlying the pathogenesis of keloids remain largely unexplored, thus limiting the development of therapeutic interventions. To screen the key molecules in keloids, microarray data were selected from three different datasets obtained from the Gene Expression Omnibus database, namely GSE145725, GSE7890 and GSE44270. One differentially expressed gene was identified, periostin (POSTN), which was upregulated in keloid fibroblasts (KFs) compared with normal fibroblasts. Its high expression was further validated in KFs using reverse transcription‑quantitative PCR (RT‑qPCR), western blotting and immunofluorescence staining. Its potential function were explored in keloids through loss-of-function assay. Notably, the EdU incorporation assay and cell cycle assay indicated that POSTN knockdown had limited effects on the proliferation of KFs; however, the RT‑qPCR, western blotting, and RNA sequencing results suggested that POSTN inhibition blocked the JAK‑STAT signaling pathway and decreased the expression levels of various proinflammatory factors in KFs. Additionally, the RT‑qPCR and western blotting results demonstrated that IL‑4 and IL‑13, two significant mediators of T helper 2 (Th2) signaling, could induce POSTN expression in KFs. Notably, IL‑4 receptor (IL‑4R), a receptor for both IL‑4 and IL‑13, could be positively modulated by POSTN through the Reactome enrichment, RT‑qPCR and western blotting analysis. Furthermore, IL‑4R was essential for IL‑4/IL‑13‑induced POSTN upregulation in KFs, thus indicating a positive feedback loop between POSTN and Th2 signaling. Overall, the current study uncovered a novel mechanism of POSTN, which could be associated with keloid inflammation, thus highlighting the POSTN/Th2 feedback loop as a potential therapeutic target for patients with keloids.