Dermatologica Sinica (Nov 2024)

The inhibitory effect of type V transforming growth factor-β receptor antagonist on the proliferation of keloid fibroblasts by suppressing insulin-like growth factor-binding protein 3-interleukin-6 signaling

  • Boya Zhou,
  • Xunxun Lin,
  • Lingling Xia,
  • Zhen Gao,
  • Meihua Di,
  • Xiaoli Wu,
  • Wenbo Wang

DOI
https://doi.org/10.4103/ds.DS-D-24-00052
Journal volume & issue
Vol. 42, no. 4
pp. 255 – 264

Abstract

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Background: Hyperplasia of fibroblasts is critical in keloid pathogenesis. Insulin-like growth factor-binding protein 3 (IGFBP3) is an important factor in the regulation of cell growth and type V transforming growth factor-β receptor (TβR-V) is a specific receptor of IGFBP3. However, the role of IGFBP3 in keloid development has not been reported. Objectives: This study aimed to investigate the role of IGFBP3 in keloid pathogenesis and evaluate the effects of TβR-V antagonist on keloid fibroblasts (KFs) activities. Methods: IGFBP3 expression in keloids and its impact on KF proliferation were examined. The effects of TβR-V antagonist on KF cell proliferation, migration, and invasion were also investigated. Differentially expressed genes (DEGs) between TβR-V antagonist treated and nontreated KFs were identified through RNA-sequencing (RNA-seq), followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein–protein interaction (PPI) network analyses. Results: IGFBP3 was overexpressed in keloids and could promote KF proliferation. TβR-V antagonist suppressed KFs proliferation, migration, and invasion. GO and KEGG analyses showed that the downregulated DEGs revealed by RNA-seq were significantly enriched in terms related to cell proliferation. Interleukin-6 (IL-6) was identified as the only gene interacting with IGFBP3 in the PPI network and was associated with nine hub genes. In vitro assay confirmed the suppression of IL-6 by TβR-V antagonist in KFs. Conclusion: Our study demonstrated that TβR-V antagonist could inhibit keloid growth likely through suppressing IGFBP3-IL-6 signaling activation. These findings suggest that targeting TβR-V could be a potential therapeutic strategy for keloid treatment.

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