TRAF3IP2 regulated by FOXO4 affects fibroblast proliferation, migration, and extracellular matrix deposition in keloid through the TGF‐β1/Smad pathway.

Background: Keloids are "tumor‐like" scars that grow beyond the boundary of injury. Its pathogenesis is complex. This paper will discuss the pathogenesis of keloid from the transcriptional regulation mechanism of TRAF3IP2. Methods: IL‐17 was utilized to induce human keloid fibroblasts (KFs) and normal dermal fibroblasts. With the application of RT‐qPCR and Western blot, TRAF3IP2 expression was detected. Subsequently, the expression of TRAF3IP2 was interfered by cell transfection and the effects of interfering TRAF3IP2 on cell proliferative rate, migration rate, and extracellular matrix were assessed with CCK‐8, Wound Healing, immunofluorescence, and Western blot techniques. Proliferation, migration, and (ECM) deposition were detected by JASPAR software predicted the binding sites of transcription factors FOXO4 and TRAF3IP2 promoters. The relationship between FOXO4 and TRAF3IP2 was verified by Dual luciferase activity assay and ChIP. Finally, the expression of TRAF3IP2 and FOXO4 was interfered simultaneously to further explore the mechanism. Results: TRAF3IP2 was enhanced in IL‐17 induced KFs. Interference with TRAF3IP2 imparted suppressive effects on the proliferation, migration, and ECM deposition of KFs. FOXO4 could inhibit TRAF3IP2 transcription, and interference with FOXO4 reversed the effect of TRAF3IP2 down‐regulation on KFs via TGF‐β1/Smad pathway. Conclusion: TRAF3IP2 was regulated by FOXO4 and affected fibroblast proliferation, migration, and ECM deposition in keloid through the TGF‐β1/Smad pathway. [ABSTRACT FROM AUTHOR]