Silent information regulator 2 (Sir2) is a nicotinamide adenine dinucleotide- (NAD+-) dependent deacetylase. The homology of SIRT1 and Sir2 has been extensively studied. SIRT1 deacetylates target proteins using the coenzyme NAD+ and is therefore linked to cellular energy metabolism and the redox state through multiple signalling and survival pathways. During the past decade, investigators have reported that SIRT1 activity is essential in cancer, neurodegenerative diseases, diabetes, cardiovascular disease, and other age-related diseases. In the kidneys, SIRT1 may inhibit renal cell apoptosis, inflammation, and fibrosis. Therefore its activation may also become a new therapeutic target in the patients with chronic kidney disease including diabetic nephropathy. In this paper, we would like to review the protective functions of sirtuins and the role of SIRT1 in the onset of kidney disease based on previous studies, including diabetic nephropathy, acute renal injury, chronic kidney disease as well as lupus nephritis.
Parkinson's disease (PD) is a prevalent neurodegenerative disease characterized by the loss of dopaminergic (DA) neurons. With their migration capacity toward the sites of diseased DA neurons in the PD brain, mesenchymal stem cells (MSCs) have the potential to differentiate to DA neurons for the replacement of damaged neurons and to secrete neurotrophic factors for the protection and regeneration of diseased DA neurons; therefore MSCs show promise for the treatment of PD. In this study, for the first time, we demonstrate that dextran-coated iron oxide nanoparticles (Dex-IO NPs) can improve the therapeutic efficacy of human MSCs (hMSCs) in a mouse model of PD induced by a local injection of 6-hydroxydopamine (6-OHDA). In situ examinations not only show that Dex-IO NPs can improve the rescue effect of hMSCs on the loss of host DA neurons but also demonstrate that Dex-IO NPs can promote the migration capacity of hMSCs toward lesioned DA neurons and induce the differentiation of hMSCs to DA-like neurons at the diseased sites. We prove that in vitro Dex-IO NPs can enhance the migration of hMSCs toward 6-OHDA-damaged SH-SY5Y-derived DA-like cells, induce hMSCs to differentiate to DA-like neurons in the conditioned media derived from 6-OHDA-damaged SH-SY5Y-derived DA-like cells and promote the protection/regeneration effects of hMSCs on 6-OHDA-damaged SH-SY5Y-derived DA-like cells. We confirm the potential of MSCs for cell-based therapy for PD. Dex-IO NPs can be used as a tool to accelerate and optimize MSC therapeutics for PD applicable clinically.
Edited by Robert Barouki
Keywords:High glucose Thioredoxin interacting protein p38 mitogen-activated protein kinase Glomerular mesangial cell a b s t r a c t Excessive reactive oxygen species (ROS) play a key role in the pathogenesis of diabetic nephropathy. The thioredoxin (TRX) system, a major thiol antioxidant system, regulates the reduction of intracellular ROS. Here we show that high glucose (HG) inhibits TRX ROS-scavenging function through p38 mitogen-activated protein kinase (MAPK)-mediated induction of thioredoxin interacting protein (TXNIP) in mouse mesangial cells (MMCs). Knockdown of TXNIP in MMCs reversed HG-induced reduction of TRX activity and inhibited HG-induced activation of p38 MAPK and increased synthesis of TGF-b1 and fibronectin. These data suggest that HG-induced overexpression of TXNIP in MMCs, which may be via the p38 MAPK pathway.
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