ABSTRACT
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 O-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.
Subject(s)
Acylation/physiology , Fibrosis/metabolism , Kidney Diseases/metabolism , Proto-Oncogene Proteins c-raf/metabolism , Acetylglucosamine/metabolism , Animals , Cell Line , Disease Models, Animal , Epithelial-Mesenchymal Transition/physiology , Humans , Male , Protein Processing, Post-Translational/physiology , Rats , Rats, Sprague-Dawley , Signal Transduction/physiology , Ubiquitination/physiology , Ureteral Obstruction/metabolismABSTRACT
Objective To discuss the application of 3D laser scanner and computer technology in restoration of the accident scene and reconstruction of the accident process, as well as identification of the driver-passenger relationship. Methods The scene of a traffic accident, the accident vehicle and the vehicle of the same type as accident vehicle were scanned using 3D laser scanner. The accident scene, traces and accident vehicle were integrated using computer technology to restore the accident scene, and the accident process was reconstructed and analyzed by combining the characteristics of the body injuries. Results By restoring the accident scene and reconstructing the accident process with 3D laser scanner, it was determined that Wu was in the driving seat at the time of the accident. Conclusion It is more objective and scientific to use 3D laser scanning technology to restore the accident scene, reconstruct the accident process and analyze the moving track of the driver and passengers in the vehicle. It will help to improve the accuracy of forensic identification of road traffic accidents.