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

2021 ◽  
Vol 22 (11) ◽  
pp. 6027
Author(s):  
Swayam Prakash Srivastava ◽  
Julie E. Goodwin ◽  
Pratima Tripathi ◽  
Keizo Kanasaki ◽  
Daisuke Koya

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

Nephron ◽  
2021 ◽  
pp. 1-11
Author(s):  
Juan D. Coellar ◽  
Jianyin Long ◽  
Farhad R. Danesh

Recent advances in large-scale RNA sequencing and genome-wide profiling projects have unraveled a heterogeneous group of RNAs, collectively known as long noncoding RNAs (lncRNAs), which play central roles in many diverse biological processes. Importantly, an association between aberrant expression of lncRNAs and diverse human pathologies has been reported, including in a variety of kidney diseases. These observations have raised the possibility that lncRNAs may represent unexploited potential therapeutic targets for kidney diseases. Several important questions regarding the functionality of lncRNAs and their impact in kidney diseases, however, remain to be carefully addressed. Here, we provide an overview of the main functions and mechanisms of actions of lncRNAs, and their promise as therapeutic targets in kidney diseases, emphasizing on the role of some of the best-characterized lncRNAs implicated in the pathogenesis and progression of diabetic nephropathy.


2021 ◽  
Vol 22 (4) ◽  
pp. 1525
Author(s):  
Chunling Huang ◽  
Ji Bian ◽  
Qinghua Cao ◽  
Xin-Ming Chen ◽  
Carol A. Pollock

Mitochondria are critical organelles that play a key role in cellular metabolism, survival, and homeostasis. Mitochondrial dysfunction has been implicated in the pathogenesis of diabetic kidney disease. The function of mitochondria is critically regulated by several mitochondrial protein kinases, including the phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1). The focus of PINK1 research has been centered on neuronal diseases. Recent studies have revealed a close link between PINK1 and many other diseases including kidney diseases. This review will provide a concise summary of PINK1 and its regulation of mitochondrial function in health and disease. The physiological role of PINK1 in the major cells involved in diabetic kidney disease including proximal tubular cells and podocytes will also be summarized. Collectively, these studies suggested that targeting PINK1 may offer a promising alternative for the treatment of diabetic kidney disease.


2020 ◽  
Vol 68 (4) ◽  
pp. 225-236
Author(s):  
Moustafa Abdalla ◽  
Mohamed Abdalla ◽  
Ferhan S. Siddiqi ◽  
Laurette Geldenhuys ◽  
Sri N. Batchu ◽  
...  

Proteomes ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 31
Author(s):  
Scott Bringans ◽  
Kirsten Peters ◽  
Tammy Casey ◽  
Jason Ito ◽  
Richard Lipscombe

PromarkerD is a proteomics derived test for predicting diabetic kidney disease that measures the concentrations of three plasma protein biomarkers, APOA4, CD5L and IBP3. Antibodies against these proteins were developed and applied to a multiplexed immunoaffinity capture mass spectrometry assay. In parallel, and facilitating current clinical laboratory workflows, a standard ELISA was also developed to measure each protein. The performance characteristics of the two technology platforms were compared using a cohort of 100 samples, with PromarkerD test scores demonstrating a high correlation (R = 0.97). These technologies illustrate the potential for large scale, high throughput clinical applications of proteomics now and into the future.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Yajing Huang ◽  
Jingwei Chi ◽  
Fanxiang Wei ◽  
Yue Zhou ◽  
Yihai Cao ◽  
...  

Diabetic kidney disease (DKD) is a common cause of end-stage renal disease, and diagnosis and treatment in time can help delay its progress. At present, there are more and more studies on the pathogenesis of DKD; mitochondrial dysfunction plays an important role in DKD. The occurrence and development of DKD is closely related to epigenetic changes and the interaction between mtDNA, ROS, inflammatory factors, and endothelial damage, which continuously aggravates kidney. The change of mtDNA is both the cause of DKD and the result of DKD. It is of great significance to incorporate the change of mtDNA into the monitoring of patients with diabetes. Existing evidence indicates that changes in mtDNA copy number in blood and urine reflect mitochondrial dysfunction and the severity of DKD. However, large-scale, long-term follow-up clinical trials are still needed to determine the threshold range. By the time, mitochondrial-targeted antioxidants will become a new method for the treatment of DKD and other diabetic complications; mtDNA also can be a therapeutic target for them.


Author(s):  
Jiten Patel ◽  
Jose Torrealba ◽  
Emilio Poggio ◽  
Jack Bebiak ◽  
Charles Alpers ◽  
...  

The Kidney Precision Medicine Project (KPMP) seeks to establish a molecular atlas of the kidney in health and disease and improve our understanding of the molecular drivers of chronic kidney disease and acute kidney injury. Herein, we describe the case of a 66-year-old woman with chronic kidney disease who underwent a protocol KPMP kidney biopsy. Her clinical history included well-controlled diabetes mellitus, hypertension, and proteinuria. The patient's histopathology was consistent with modest hypertension-related kidney injury, without overt diabetic kidney disease (DKD). Transcriptomic signatures of the glomerulus, interstitium, and tubular subsegments were obtained from laser microdissected tissue. The molecular signatures uncovered revealed evidence of early DKD adaptation and ongoing active tubular injury with enriched pathways related to mesangial cell hypertrophy, glycosaminoglycan biosynthesis, and apoptosis. Molecular evidence of DKD was found across the nephron. Novel molecular assays can supplement and enrich the histopathologic diagnosis obtained from a kidney biopsy.


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