Diabetic kidney disease (DKD) is among the most common complications of diabetes mellitus (DM), and remains the leading cause of end-stage renal diseases (ESRDs) in developed countries, with no definitive therapy yet available. It is imperative to decipher the exact mechanisms underlying DKD and identify novel therapeutic targets. Burgeoning evidence indicates that long non-coding RNAs (lncRNAs) are essential for diverse biological processes. However, their roles and the mechanisms of action remain to be defined in disease conditions like diabetes and DKD. The pathogenesis of DKD is twofold, so is the principle of treatments. As the underlying disease, diabetes per se is the root cause of DKD and thus a primary focus of therapy. Meanwhile, aberrant molecular signaling in kidney parenchymal cells and inflammatory cells may directly contribute to DKD. Evidence suggests that a number of lncRNAs are centrally involved in development and progression of DKD either via direct pathogenic roles or as indirect mediators of some nephropathic pathways, like TGF-β1, NF-κB, STAT3 and GSK-3β signaling. Some lncRNAs are thus likely to serve as biomarkers for early diagnosis or prognosis of DKD or as therapeutic targets for slowing progression or even inducing regression of established DKD. Here, we elaborated the latest evidence in support of lncRNAs as a key player in DKD. In an attempt to strengthen our understanding of the pathogenesis of DKD, and to envisage novel therapeutic strategies based on targeting lncRNAs, we also delineated the potential mechanisms of action as well as the efficacy of targeting lncRNA in preclinical models of DKD.
Diabetic kidney disease (DKD) is one of the most common microvascular complication of both type 1 (T1DM) and type 2 diabetes mellitus (T2DM), and the leading cause of end-stage renal disease (ESRD) worldwide. Persistent inflammation and subsequent chronic fibrosis are major causes of loss of renal function, which is associated with the progression of DKD to ESRD. In fact, DKD progression is affected by a combination of genetic and environmental factors. Approximately, one-third of diabetic patients progress to develop DKD despite intensive glycemic control, which propose an essential concept “metabolic memory.” Epigenetic modifications, an extensively studied mechanism of metabolic memory, have been shown to contribute to the susceptibility to develop DKD. Epigenetic modifications also play a regulatory role in the interactions between the genes and the environmental factors. The epigenetic contributions to the processes of inflammation and fibrogenesis involved in DKD occur at different regulatory levels, including DNA methylation, histone modification and non-coding RNA modulation. Compared with genetic factors, epigenetics represents a new therapeutic frontier in understanding the development DKD and may lead to therapeutic breakthroughs due to the possibility to reverse these modifications therapeutically. Early recognition of epigenetic events and biomarkers is crucial for timely diagnosis and intervention of DKD, and for the prevention of the progression of DKD to ESRD. Herein, we will review the latest epigenetic mechanisms involved in the renal pathology of both type 1 (T1DN) and type 2 diabetic nephropathy (T2DN) and highlight the emerging role and possible therapeutic strategies based on the understanding of the role of epigenetics in DKD-associated inflammation and fibrogenesis.
Diabetic nephropathy (DN), one of the most common and severe microvascular complications of diabetes mellitus (DM), is an important risk factor for DM patient’s death. Nowadays, DN has become the leading cause of end-stage renal disease (ESRD) in most countries without effective therapeutic methods. Recently, the renoprotective effects mediated by vitamin D (VD) and vitamin D receptor (VDR) have been evidenced. VD, a kind of steroid with the active form 1,25(OH)2D3, has been known for the crucial roles in the modulation of serum calcium and phosphorus concentrations. It exerts important functions by binding with its receptor VDR.VDR, a transcription factor located at chromosome 12 containing 9 exons, is one of the nonsteroid nuclear hormone receptor superfamily, which participates in transcriptional regulation of genes in tissue- and cell-specific ways. Increasing evidences have demonstrated that VD/VDR signaling pathway possesses a variety of kidney-protective effects in DN patients, such as antiproteinuria, antifibrosis, anti-inflammatory, and preventing podocyte damage. Although there are many studies on the role of the VD/VDR signaling pathway in DN, the effects and mechanisms still need to be further explained. This review summarized the multiple roles of VD/VDR in podocyte injury, tubule lesions, interstitial fibrosis, and inflammation, as well as the clinical applications about DN to explore much more and effective therapeutic methods for DN.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.