The expression of NOTUM in replantation of severed fingers may be an important treatment factor.

BACKGROUND: After years of development, digital replantation has become a mature treatment. Although the NOTUM gene has been shown to be involved in the formation of vertebrate nerves, whether it contributes to the osteogenic mechanism of severed finger replantation remains unknown. In response to this, this study investigates the specific details of NOTUM involvement in replantation of severed fingers. METHODS: The experimental subjects are patients with replantation of severed fingers from Shulan International Medical College of Shulan (Hangzhou) Hospital affiliated to Zhejiang Shuren University. In addition to using bone marrow mesenchymal stem cells (BMSCs) as an in vitro system, this experiment also involves quantitative polymerase chain reaction, microarray analysis, cell counting Kit-8, ethynyl deoxyuridine staining and Western blot analysis. RESULTS: The expression level of NOTUM in the severed finger replantation group is lower than that in the normal group. NOTUM inhibits cell growth and cell transfer, osteogenic differentiation and ß-catenin gene expression in BMSCs. Luciferase reporter assay illustrated that ß-catenin wild type closely correlated with NOTUM. The inhibition of ß-catenin increases the effects of NOTUM on cell growth, cell transfer and osteogenic differentiation of BMSCs. CONCLUSIONS: Considering that NOTUM can inhibit cell growth, cell transfer, osteogenic differentiation of BMSCs, as well as the gene expression of ß-catenin, it may be a biomarker of osteogenic differentiation and a potential therapeutic target for replantation of severed fingers.

TRAF3IP2 regulated by FOXO4 affects fibroblast proliferation, migration, and extracellular matrix deposition in keloid through the TGF-ß1/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-ß1/Smad pathway. CONCLUSION: TRAF3IP2 was regulated by FOXO4 and affected fibroblast proliferation, migration, and ECM deposition in keloid through the TGF-ß1/Smad pathway.