Long Noncoding RNAs and Their Therapeutic Promise in Diabetic Nephropathy

Coellar, Juan D; Jiang, Long; Danesh, Farhad R.

doi:10.1159/000515422

Cited by 17 publications

(14 citation statements)

References 104 publications

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“…More and more studies have demonstrated that lncRNA exerts a crucial role in various kinds of physiopathological processes such as genomic imprinting, gene expression, cell proliferation, tumorigenesis (de Oliveira et al, 2019, Bach and Lee, 2018, Sakatani et al, 2005). As expected, lncRNAs are abnormally expressed in DN patients and mice and exert an important role in the progression of DN (Coellar et al, 2021). The data from RNA sequencing show that 106 lncRNAs are dys-regulated in kidney tissues of DN mice and 42 lncRNAs are correlated with DN (Li et al, 2018).…”

Section: Introductionsupporting

confidence: 66%

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Long non-coding RNA L13Rik promotes high glucose-induced mesangial cell injury by regulating miR-2861/CDKN1B axis

Sun

Ding

Chen

et al. 2022

Preprint

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Diabetic nephropathy (DN) is a frequent and severe microvascular complication of diabetes. Glomerular mesangial cell (MC) injury occurs at the initial phase of DN and acts as a critical role in the pathogenesis of DN. Given the importance of long non coding RNA (lncRNA) in regulating MC hyperplasia and extracellular matrix (ECM) accumulation, it is essential to identify functional lncRNAs during MC injury. Here a novel lncRNA, C920021L13Rik (L13Rik for short), was identified to up-regulated in DN progression. The expression of L13Rik in DN patients and diabetic rats was assessed using quantitative real-time PCR (qRT-PCR), and the function of L13Rik on regulating HG-induced MC injury was assessed using cell counting kit-8 (CCK-8) and western blot assay to analyze MC viability and ECM accumulation. We found that L13Rik level was significantly increased while miR-2861 level was significantly decreased in peripheral blood of DN patients, renal tissues of diabetic rats, and HG-treated MCs. Functionally, both L13Rik depletion and miR-2861 overexpression effectively reduced HG-induced MC survival, ECM accumulation, and cell hypertrophy. Mechanistically, L13Rik functioned as a competing endogenous RNA (ceRNA) to sponge miR-2861, resulting in the de-repression of its target cyclin-dependent kinase inhibitor 1B (CDKN1B), a gene known to accelerate MC injury. Collectively, the current results demonstrate that up-regulated L13Rik is correlated with DN, and may be a hopeful therapeutic target for DN.

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Section: Introductionsupporting

confidence: 66%

“…MC injury, including hyperplasia, ECM production, and hypertrophy, plays a crucial role in the pathology of DN (Dai et al, 2017). LncRNA was reported to be involved in MC injury and DN progression (Coellar et al, 2021). However, the role of lncRNA in these processes is still unclear.…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA L13Rik promotes high glucose-induced mesangial cell injury by regulating miR-2861/CDKN1B axis

Sun

Ding

Chen

et al. 2022

Preprint

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“…GAS5-lncRNA is a snoRNA host gene which encodes a large number of snoRNAs. In addition, a number of studies have linked this lncRNA to kidney function (42)(43)(44). Interestingly, this lncRNA is also a binding partner for SNORD118 described above (45).…”

Section: Members Of Other Srna Classesmentioning

confidence: 99%

Small RNA sequencing reveals snoRNAs and piRNA-019825 as novel players in diabetic kidney disease

Hart

Bouland

Klerk

et al. 2022

Preprint

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Aims/hypothesis Micro- and macrovascular complications are common among persons with type 2 diabetes. Interest into the potential of circulating small non-coding RNAs (sRNAs) as biomarkers or drivers of the development of diabetic complications is growing. In this study we investigated if circulating sRNAs levels associate with prevalent chronic kidney disease (CKD) in persons with type 2 diabetes. Methods Plasma sRNAs levels were determined using sRNA-seq, allowing detection of miRNAs, snoRNAs, piRNAs, tRNA-fragments and various other sRNA classes, in persons with type 2 diabetes, with CKD (n=69) or without CKD (n=405). Multiple regression analyses were used to test for associations between the sRNAs and primary endpoint CKD. In secondary analyses, we also tested the association with eGFR and albuminuria (UACR). Results In total, twelve sRNA were associated with prevalent CKD (logFC = -0.32 to -1.28, all P≤6.24x10-4). Although miRNAs represent the majority of the sRNAs measured (64%) only four miRNA were significantly associated with prevalent CKD. Interestingly, the majority of the significant sRNA belonged to the snoRNAs (58%). Similar results were observed for eGFR and UACR. Only one of the twelve sRNAs showed its highest expression in kidney whereas several others showed high expression in liver or colon. Conclusions/interpretation Small RNAs present in the circulation associate with CKD in persons with type 2 diabetes. Further studies are warranted to elucidate the biological role of sRNA in diabetic CKD and in particular snoRNAs. High expression of these circulating sRNAs in tissues other than kidney suggest a role in inter-organ communication.

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“…Available evidence has indicated the important roles of lncRNAs in the pathophysiology of diabetic kidney disease (DKD), and the crosstalk between lncRNAs and DKD were reported in recent years [15][16][17][18][19]. Altered expression levels of lncRNAs play key roles in the development of proteinuria and associated diabetic nephropathy (DN) [15,20].…”

Section: Lncs In Diabetic Kidney Diseasementioning

confidence: 99%

Interactions among Long Non-Coding RNAs and microRNAs Influence Disease Phenotype in Diabetes and Diabetic Kidney Disease

Srivastava

Goodwin

Tripathi

et al. 2021

IJMS

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Large-scale RNA sequencing and genome-wide profiling data revealed the identification of a heterogeneous group of noncoding RNAs, known as long noncoding RNAs (lncRNAs). These lncRNAs play central roles in health and disease processes in diabetes and cancer. The critical association between aberrant expression of lncRNAs in diabetes and diabetic kidney disease have been reported. LncRNAs regulate diverse targets and can function as sponges for regulatory microRNAs, which influence disease phenotype in the kidneys. Importantly, lncRNAs and microRNAs may regulate bidirectional or crosstalk mechanisms, which need to be further investigated. These studies offer the novel possibility that lncRNAs may be used as potential therapeutic targets for diabetes and diabetic kidney diseases. Here, we discuss the functions and mechanisms of actions of lncRNAs, and their crosstalk interactions with microRNAs, which provide insight and promise as therapeutic targets, emphasizing their role in the pathogenesis of diabetes and diabetic kidney disease

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Long Noncoding RNAs and Their Therapeutic Promise in Diabetic Nephropathy

Cited by 17 publications

References 104 publications

Long non-coding RNA L13Rik promotes high glucose-induced mesangial cell injury by regulating miR-2861/CDKN1B axis

Long non-coding RNA L13Rik promotes high glucose-induced mesangial cell injury by regulating miR-2861/CDKN1B axis

Small RNA sequencing reveals snoRNAs and piRNA-019825 as novel players in diabetic kidney disease

Interactions among Long Non-Coding RNAs and microRNAs Influence Disease Phenotype in Diabetes and Diabetic Kidney Disease

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