Epigenetic regulation of Toll-like receptors 2 and 4 in kidney disease

Abstract

Kidney disease affects more than 10% of the worldwide population and causes significant morbidity and mortality. Epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNAs (ncRNAs) play a pivotal role in the progression of kidney disease. These epigenetic mechanisms are reversible and majorly involved in regulating gene expression of inflammatory, fibrotic, and apoptotic proteins. Emerging data suggest that the Toll-like receptor 2 and Toll-like receptor 4 (TLR2 and TLR4) are expressed by almost all types of kidney cells and known for promoting inflammation by recognizing damage-associated molecular proteins (DAMPs). Epigenetic mechanisms regulate TLR2 and TLR4 signaling in various forms of kidney disease where different histone modifications promote the transcription of the TLR2 and TLR4 gene and its ligand high mobility group box protein 1 (HMGB1). Moreover, numerous long non-coding RNAs (LncRNAs) and microRNAs (miRNAs) modulate TLR2 and TLR4 signaling in kidney disease. However, the precise mechanisms behind this regulation are still enigmatic. Studying the epigenetic mechanisms involved in the regulation of TLR2 and TLR4 signaling in the development of kidney disease may help in understanding and finding novel therapeutic strategies. This review discusses the intricate relationship of epigenetic mechanisms with TLR2 and TLR4 in different forms of kidney diseases. In addition, we discuss the different lncRNAs and miRNAs that regulate TLR2 and TLR4 as potential therapeutic targets in kidney disease.