Emerging Roles of Long Non-Coding RNAs in Renal Fibrosis

Abstract

Renal fibrosis is an unavoidable consequence that occurs in nearly all of the nephropathies. It is characterized by a superabundant deposition and accumulation of extracellular matrix (ECM). All compartments in the kidney can be affected, including interstitium, glomeruli, vasculature, and other connective tissue, during the pathogenesis of renal fibrosis. The development of this process eventually causes destruction of renal parenchyma and end-stage renal failure, which is a devastating disease that requires renal replacement therapies. Recently, long non-coding RNAs (lncRNAs) have been emerging as key regulators governing gene expression and affecting various biological processes. These versatile roles include transcriptional regulation, organization of nuclear domains, and the regulation of RNA molecules or proteins. Current evidence proposes the involvement of lncRNAs in the pathologic process of kidney fibrosis. In this review, the biological relevance of lncRNAs in renal fibrosis will be clarified as important novel regulators and potential therapeutic targets. The biology, and subsequently the current understanding, of lncRNAs in renal fibrosis are demonstrated—highlighting the involvement of lncRNAs in kidney cell function, phenotype transition, and vascular damage and rarefaction. Finally, we discuss challenges and future prospects of lncRNAs in diagnostic markers and potential therapeutic targets, hoping to further inspire the management of renal fibrosis.

EndMT Regulation by Small RNAs in Diabetes-Associated Fibrotic Conditions: Potential Link With Oxidative Stress

“…Hence, lncRNAs are involved in a variety of human diseases where they appear differentially expressed or genetically perturbed ( Harries, 2012 ; Shi et al, 2013 ). In this context, most of the knowledge pertaining to lncRNAs is derived from cancer however there is increasing evidence of their involvement in other conditions, such as Alzheimer’s disease, diabetes, cardiac complications ( DiStefano, 2018 ; Greco et al, 2018 ; Leung and Natarajan, 2018 ) and fibrosis ( He Z. et al, 2020 ; Li et al, 2020a ; Lin J. et al, 2020 ). One important function of lncRNAs is their role as a molecular sponge to certain miRNAs, hindering their expression ( Biswas et al, 2018 ).…”

The Pathogenesis of End-Stage Renal Disease from the Standpoint of the Theory of General Pathological Processes of Inflammation

“…Renal fibrosis is a typical final stage of inflammation that occurs in nearly all nephropathies [ 25 ]. Fibrosis can affect all compartments of the kidney, ultimately causing destruction of the renal parenchyma and leading to ESRD [ 26 ].…”

“…Negative dynamics of DKD is largely determined by the severity of proinflammatory stress in endotheliocytes and podocytes, including activation of the following signaling pathways: intercellular contact receptors Notch-1; membrane GTP-binding proteins; stress protein kinases MAPK (mitogen-activated protein kinase) and mTORC1 (mammalian target of rapamycin); many stress miRNAs and long non-coding (regulatory) RNAs; heat-shock proteins, especially HSP70; various proapoptotic factors; other factors of cellular stress, including chemokines, growth factors, and TGF-β1 [ 25 , 93 , 144 , 152 ]. …”

“…other factors of cellular stress, including chemokines, growth factors, and TGF-β1 [ 25 , 93 , 144 , 152 ].…”

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

“…Altered expression levels of lncRNAs play key roles in the development of proteinuria and associated diabetic nephropathy (DN) [ 15 , 20 ]. LncRNAs are involved in the progression of kidney disease through regulation of many important factors, such as pathologic processes in mesangial cells, podocytes, reactive oxidative species, epithelial-to-mesenchymal transition (EMT), endothelial-to-mesenchymal transitions (EndMT) and actions on microRNAs [ 21 , 22 , 23 ].…”