ABSTRACT
palmitoylation, a reversible post-translational modification, is initiated by the DHHC family of palmitoyltransferases and reversed by several acyl protein thioesterases. However, the role and mechanisms for protein palmitoylation in renal fibrosis have not been elucidated. Here we show protein palmitoylation and DHHC9 were downregulated in the fibrotic kidneys of mouse models and chronic kidney disease (CKD) patients. Ablating DHHC9 in tubular cells aggravated, while inducing DHHC9 overexpression with adeno-DHHC9 transfection or iproniazid treatment protected against kidney fibrosis in male mouse models. Mechanistically, DHHC9 palmitoylated ß-catenin, thereby promoted its ubiquitination and degradation. Additionally, acyl protein thioesterase 1 (APT1) was induced in the fibrotic kidneys, which depalmitoylated ß-catenin, increased its abundance and nuclear translocation. Ablating tubular APT1 or inhibiting APT1 with ML348 markedly protected against unilateral ureter obstruction (UUO) or ischemia/reperfusion injury (IRI)-induced kidney fibrosis in male mice. This study reveals the regulatory mechanism of protein palmitoylation in kidney fibrosis.
Subject(s)
Renal Insufficiency, Chronic , Ureteral Obstruction , Humans , Male , Mice , Animals , beta Catenin , Lipoylation , Renal Insufficiency, Chronic/pathology , Ureteral Obstruction/complications , Ureteral Obstruction/pathology , Fibrosis , Kidney/pathologyABSTRACT
Energy metabolism is crucial in maintaining cellular homeostasis and adapting to stimuli for tubular cells. However, the underlying mechanisms remain largely unknown. Here, we report that PP2Acα was upregulated in damaged tubular cells from patients and animal models with acute or chronic kidney injury. Using in vitro and in vivo model, we demonstrated that PP2Acα induction in damaged tubular cells suppresses fatty acid oxidation and promotes glycolysis, leading to cell death and fibrosis. Mechanistically, we revealed that PP2Acα dephosphorylates ACC through interaction with B56δ, leading to the regulation of fatty acid oxidation. Furthermore, PP2Acα also dephosphorylates p-Glut1 (Thr478) and suppresses Trim21-mediated Glut1 ubiquitination and degradation, leading to the promotion of glucose intake and glycolysis. Thus, this study adds new insight into the tubular cell metabolic alterations in kidney diseases. PP2Acα may be a promising therapeutic target for kidney injury.
Subject(s)
Glycolysis , Kidney , Animals , Fatty Acids , Glucose Transporter Type 1 , Phosphoprotein PhosphatasesABSTRACT
To solve the inspection problems in cotton storage, as well as the need for environmental monitoring in the process of modern cotton bale storage, an intelligent inspection and temperature and humidity intelligent monitoring system based on RFID cotton bale was developed by adopting RFID (Radio Frequency Identification) technology, wireless temperature and humidity real-time monitoring technology and handheld terminal intelligent inspection technology. The system was composed of RFID positioning inspection module and temperature and humidity real-time monitoring and transmission module. The artificial neural network (ANN) based on the particle swarm optimization (PSO) algorithm was used to process the monitoring data of the system by Gaussian filtering, and an accurate classification model of RSSI and label position was established. The test results showed that: Through the comparative analysis of the RFID indoor positioning algorithm, the positioning error of the PSO-ANN algorithm was small. In the actual cotton bale warehouse test, the relative error of positioning and monitoring for RFID cotton bale intelligent inspection and monitoring system was less than 6.7%, which effectively improved the working efficiency of inspection personnel and the security of cotton bale storage. The relative error of temperature and humidity was less than 8% and less than 7%, which could display the temperature and humidity information in real time and meet the real-time demand. This study improved the management personnel's effective positioning and inspection of the cotton bale, prevented the loss of cotton bale, reduced the deterioration probability of cotton bale, and effectively improved the storage management level of the cotton bale. It was of great practical significance to realize the networking, automation, and intelligence of cotton bale storage management.
