Anti-CTNNB1 (mutation T41I) Monoclonal Antibody, clone XH033

Fibroblast-like synoviocytes (FLSs) participate in the pathogenesis of rheumatoid arthritis (RA). Emerging evidence has highlighted the role of long non-coding RNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and its potential involvement in RA. In this study, we test the hypothesis that the MALAT1 might inhibit proliferation and inflammatory response of FLSs in RA. The expression of MALAT1 was examined in synovial tissues from patients with RA. The effect of MALAT1 on cultured FLSs was analyzed by introducing overexpressed MALAT1 or short hairpin RNA (shRNA) against MALAT1. To validate whether methylation of CTNNB1 promoter was affected by MALAT1 alternation, we assessed the recruitment of DNA methyltransferases to CTNNB1 promoter. In cultured FLSs with shRNA-mediated CTNNB1 knockdown or activated Wnt signaling, we found the interaction between CTNNB1 and Wnt signaling. MALAT1 expression was reduced in synovial tissues of RA. MALAT1 could bind to CTNNB1 promoter region and recruit methyltransferase to promote CTNNB1 promoter methylation, thereby inhibiting CTNNB1. Notably, MALAT1 could suppress the transcription and expression of CTNNB1, thereby modulating the Wnt signaling pathway. Silenced MALAT1 stimulated the nucleation of beta-catenin and the secretion of inflammatory cytokines including interleukin-6, interleukin-10, and tumor necrosis factor-alpha. Additionally, shRNA-mediated MALAT1 silencing elevated proliferation and suppressed apoptosis of FLSs accompanied. These findings provide evidence for the inhibitory effect of MALAT1 on proliferation and inflammation of FLSs by promoting CTNNB1 promoter methylation and inhibiting the Wnt signaling pathway. Therefore, this study provides a candidate therapeutic target for RA.

Background/Aim: The insulin-like growth factor 1 (IGF1) signaling pathway as an aging mechanism related to p53 in human melanogenesis remains unclear. The aim of this study was to investigate the relationship between p53 and IGF1 signaling pathway in young, senescent and H2O2-treated cells. Materials and Methods: The protein and gene expression in young, senescent and H2O2-treated cells were analyzed using western blot and reverse transcription polymerase chain reaction (RT-PCR) assays, respectively. Results: The expression levels of (phosphoinositide 3-kinases) PI3K, v-akt murine thymoma viral oncogene homolog 1 (AKT1), mammalian target of rapamycin, beta-catenin (CTNNB1), acetylated p53 (ac-p53), p53 and p-p21 proteins, related to IGF1 and p53 signaling pathways, were higher in senescent and H2O2-treated cells than those of young cells. Furthermore, AKT reduced melanogenesis through microphthalmia-associated transcription factor (MITF) inactivation by the inhibition of CTNNB1. The gene expression levels of PI3K, TP53 and catalase (CAT) in senescent and H2O2-treated cells were increased compared to young cells. Conclusion: p53 protein plays a key role in the aging of melanocytes via IGF1 signaling pathways.