MicroRNAs as Regulators of Immune and Inflammatory Responses: Potential Therapeutic Targets in Diabetic Nephropathy

Abstract

Diabetic nephropathy (DN) is the principal cause of end-stage renal disease and results in high morbidity and mortality in patients, causing a large socioeconomic burden. Multiple factors, such as metabolic abnormalities, inflammation, immunoregulation and genetic predisposition, contribute to the pathogenesis of DN, but the exact mechanism is unclear, and the therapeutic strategies are not satisfactory. Accordingly, there is an unmet need for new therapeutic targets and strategies for DN. MicroRNAs (miRNAs) act as major epigenetic mechanisms that regulate gene expression and provide novel insights into our understanding of the molecular and signaling pathways that are associated with various diseases, including DN. Studies in the past decade have shown that different miRNAs affect the progression of DN by modulating different aspects of immune and inflammatory responses. Therefore, in this review, we summarized the pivotal roles of miRNAs in inflammatory and immune processes, with an integrative comprehension of the detailed signaling network. Additionally, we discussed the possibilities and significance of these miRNAs as therapeutic targets in the treatment of DN. This review will facilitate the identification of new therapeutic targets and novel strategies that can be translated into clinical applications for DN treatment.

Complement C7 is Specifically Expressed in Mesangial Cells and is a Potential Diagnostic Biomarker for Diabetic Nephropathy and is Regulated by miR-494-3p and miR-574-5p

“… 42 , 43 In recent years, studies have revealed that some miRNAs could be regulators of immune and inflammatory responses and are potential therapeutic targets in DN. 15 , 16 Single nucleotide polymorphisms of miRNA-related genes can affect the production, expression, and function of mature miRNAs, thus affecting disease susceptibility and the immune response. We identified the differentially expressed miRNAs in DN using the GSE161884 dataset.…”

“… 14 Studies have revealed that some miRNAs could be regulators of immune and inflammatory responses and are potential therapeutic targets in DN. 15 , 16 However, there have been few studies on genetic variation in miRNA and complement levels in diabetic nephropathy.…”

Cadherin and Wnt signaling pathways as key regulators in diabetic nephropathy

“…In addition, it is noteworthy to be mentioned that non-coding RNAs (ncRNAs) that are located in the seven cytogenetic regions identified from the meta-analysis could further regulate gene expression. Roles of microRNA (miRNA), long ncRNA (lncRNA) and circular RNA (circRNA) in DN have recently studied [ 65 – 67 ]. MiRNA is the best characterized non-coding RNA for transcriptional gene regulation.…”

Epigenetics and Inflammation in Diabetic Nephropathy

“…Non-coding RNAs (ncRNAs) commonly include transfer RNA, ribosomal RNA, long ncRNA (lncRNA), small ncRNA (e.g., microRNA, piRNAs, snoRNA, snRNA, exRNA) and circular RNA (circRNA) ( Storz, 2002 ; Yang, 2015 ). Roles of microRNA (miRNA), lncRNA and circRNA in DN have been recently studied ( Loganathan et al, 2020 ; Zhou et al, 2021 ). MiRNA is the best characterized non-coding RNA for transcriptional gene regulation by targeting the 3′-UTR of a specific mRNA.…”

“…MiRNAs play significant roles in regulating inflammation in DN ( Zhou et al, 2021 ). Recent studies involving models of DN podocytes have found that downregulation of the miR-17∼92 cluster ameliorates inflammation and podocyte injury by targeting ABCA1 (ATP-binding cassette transporter A1) ( Fan et al, 2020 ).…”