Anti-RAF1 monoclonal antibody, clone TQN326

Epithelial-mesenchymal transition (EMT) is considered to be one of the most important mechanisms for the progression of renal interstitial fibrosis (RIF). Recently the relationship between post-translational modifications and EMT has been reported. O-GlcNAcylation, one of the key post-translational modifications, was rarely mentioned about its role in EMT, especially in EMT during the process of RIF. The current study aimed to determine whether O-GlcNAcylation participates in the regulation of EMT during RIF. We proved that O-GlcNAcylation prompted the EMT of HK2 cells. Mass spectral analysis identified RAF1 to be one of the O-GlcNAcylated proteins. Moreover, O-GlcNAcylation of RAF1 stabilized RAF1 protein and prompted EMT of HK2 cells. In terms of mechanism, we verified that 0-GlcNAcylation of RAF1 inhibited its ubiquitination and thus stabilized RAF1. The upregulation of RAF1 and O-GlcNAcylation products (O-GlcNAc) in vivo were also observed in unilateral ureteral obstruction (UUO) animal models. Collectively, our study indicated that O-GlcNAcylation suppressed the ubiquitination of RAF1, stabilized RAF1 and then modulated the EMT in HK2 cells. These results may give us several new targets for the treatment of RIF.

Hearing loss (HL) is one of the most frequent clinical manifestations of patients who suffer with multi-systemic genetic disorders. HL in association with other physical stigmata is referred to as a syndromic form of HL. LEOPARD syndrome (LS) is one of the disorders with syndromic HL and it is caused by a mutation in the PTPN11 or RAF1 gene. In general, 5 year old children who undergo cochlear implantation usually show a marked change in behavior regarding sound detection within the first 6 months of implant use, but word identification may not be exhibited for at least another 6-12 months of implant use. We herein report on a 5-year-old girl with LS. Her clinical manifestations including bilateral sensorineural EEL, which indicated the diagnosis of LS. We confirmed the diagnosis by identifying a disease-causing mutation in the PTPN11 gene, which was a heterozygous missense mutation Ala461Thr (c.1381G>A). She underwent cochlear implantation (Cl) without complications and she is currently on regular follow-up at postoperative 1 year. This is the first reported case of CI in a patient with LS in the medical literature.