Long Non-Coding RNAs in the Pathogenesis of Diabetic Kidney Disease

Abstract

Diabetic kidney disease (DKD) is one of the major microvascular complications of diabetes mellitus, with relatively high morbidity and mortality globally but still in short therapeutic options. Over the decades, a large body of data has demonstrated that oxidative stress, inflammatory responses, and hemodynamic disorders might exert critical influence in the initiation and development of DKD, whereas the delicate pathogenesis of DKD remains profoundly elusive. Recently, long non-coding RNAs (lncRNAs), extensively studied in the field of cancer, are attracting increasing attentions on the development of diabetes mellitus and its complications including DKD, diabetic retinopathy, and diabetic cardiomyopathy. In this review, we chiefly focused on abnormal expression and function of lncRNAs in major resident cells (mesangial cell, endothelial cell, podocyte, and tubular epithelial cell) in the kidney, summarized the critical roles of lncRNAs in the pathogenesis of DKD, and elaborated their potential therapeutic significance, in order to advance our knowledge in this field, which might help in future research and clinical treatment for the disease.

The role of long non‐coding RNAs in the development of diabetic kidney disease and the involved clinical application

“…Pathologic changes such as decreased podocyte density and structural or functional abnormalities of podocytes after podocyte injury can lead to albuminuria 75 . It is now known that DKD‐related lncRNAs influence podocyte injury caused by DKD 76 …”

Vascular complications of diabetes: A narrative review

“…For instance, the potential mechanisms of long noncoding RNAs in the development of diabetic nephropathy (DN) and DR, which relates to the roles of long noncoding RNAs in mesangial cells proliferation and fibrosis, inflammatory processes, extracellular matrix accumulation in the glomeruli and tubular injury, as well as the role of abnormal neovascularization and neuronal dysfunction. [ 4 , 5 ] nonalcoholic fatty liver disease (NAFLD) was viewed both as a driving force and a consequence of the DM. [ 6 ] Meanwhile, accumulating evidence suggests that the presence of microvascular complications (including DR, DN, and peripheral neuropathy) was inversely associated with NAFLD among hospitalized patients with type 2 diabetes.…”

No Genetic Causality between Branched-Chain Amino Acids and Diabetic Nephropathy: A Two-Sample Mendelian Randomization Study

“…Diabetic nephropathy (DN), one of the most common microvascular complications of diabetes, has been the leading cause of chronic kidney disease worldwide [1]. The pathogenesis of DN involves complex pathophysiological processes, including insulin resistance, glucolipid metabolism disorders, long-term chronic in ammation, oxidative stress, and endothelial dysfunction [2]. At present, controlling blood glucose and blood pressure plus the usage of the blockade of the renin-angiotensin-aldosterone system are the main approaches to treat DN [3], however, the risk of disease progression to end-stage renal disease remains very high.…”