Long Non-coding RNA: An Emerging Contributor and Potential Therapeutic Target in Renal Fibrosis

Abstract

Renal fibrosis (RF) is a pathological process that culminates in terminal renal failure in chronic kidney disease (CKD). Fibrosis contributes to progressive and irreversible decline in renal function. However, the molecular mechanisms involved in RF are complex and remain poorly understood. Long non-coding RNAs (lncRNAs) are a major type of non-coding RNAs, which significantly affect various disease processes, cellular homeostasis, and development through multiple mechanisms. Recent investigations have implicated aberrantly expressed lncRNA in RF development and progression, suggesting that lncRNAs play a crucial role in determining the clinical manifestation of RF. In this review, we comprehensively evaluated the recently published articles on lncRNAs in RF, discussed the potential application of lncRNAs as diagnostic and/or prognostic biomarkers, proposed therapeutic targets for treating RF-associated diseases and subsequent CKD transition, and highlight future research directions in the context of the role of lncRNAs in the development and treatment of RF.

Keywords: diabetic nephropathy; fibrosis; kidney disease; long non-coding RNA; renal fibrosis.

FIGURE 1

Mechanisms of action of lncRNA. (A) Molecular signal model: lncRNAs act as signaling pathway modulators to influence gene regulation in response to different stimuli. (B) Molecular decoy model: lncRNAs competitively bind to some RNA or proteins, causing the target to free a specific DNA region or protein, and then regulate the normal function. (C) Molecular guide model: lncRNAs interact with transcription factors or transcriptional regulators to guide transcription complexes to specific sites in the genome. (D) Molecular scaffold model: lncRNAs serve as a scaffold to bind two or more macromolecules (e.g., proteins, DNA, or other RNA species) and bring them into close proximity to chromatin.

FIGURE 2

Role of lncRNAs in RF. Also shown is that lncRNA could affect ECM accumulation, EMT process, inflammatory responses, apoptosis, cell proliferation and cell damage, and cell viability in RF.