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

Abstract

Large-scale RNA sequencing and genome-wide profiling data revealed the identification of a heterogeneous group of noncoding RNAs, known as long noncoding RNAs (lncRNAs). These lncRNAs play central roles in health and disease processes in diabetes and cancer. The critical association between aberrant expression of lncRNAs in diabetes and diabetic kidney disease have been reported. LncRNAs regulate diverse targets and can function as sponges for regulatory microRNAs, which influence disease phenotype in the kidneys. Importantly, lncRNAs and microRNAs may regulate bidirectional or crosstalk mechanisms, which need to be further investigated. These studies offer the novel possibility that lncRNAs may be used as potential therapeutic targets for diabetes and diabetic kidney diseases. Here, we discuss the functions and mechanisms of actions of lncRNAs, and their crosstalk interactions with microRNAs, which provide insight and promise as therapeutic targets, emphasizing their role in the pathogenesis of diabetes and diabetic kidney disease

Kidney microRNA Expression Pattern in Type 2 Diabetic Nephropathy in BTBR Ob/Ob Mice

“…Apart from miRNAs, other non-coding RNAs have been postulated to regulate gene expression in DN. In this way, long-noncoding RNAs (lncRNAs) and circular RNAs have been described to act as miRNA sponges, regulating their actions in DN ( Srivastava et al, 2021a ; Patil et al, 2021 ). For instance, lncRNAs NR_033515, NEAT1, OIP5-AS1, and MALAT1 promote EMT and fibrosis by sponging anti-fibrotic miRNAs ( Gao et al, 2018 ; Liu et al, 2019 ; Wang et al, 2019 ; Li N. et al, 2020 ; Fu et al, 2020 ; Meng et al, 2020 ), whereas other lncRNAs, such as ZEB1-AS1, prevent EMT and fibrosis in DN ( Meng et al, 2020 ).…”

Bibliometric Study of Trends in the Diabetic Nephropathy Research Space from 2016 to 2020

“…Several studies have highlighted links between specific miRNAs and the pathogenesis, early diagnosis, and treatment of DN [ 7 , 35 , 36 ]. Moreover, there is evidence that exosomes and associated miRNAs can impact renal tissues either directly or in synergy with other factors to shape the development and progression of DN [ 37 , 38 ]. Signal transduction pathways and associated regulatory networks are important areas of DN-related research that offer important insight into the etiological basis for this debilitating condition [ 39 – 41 ].…”

Immunohistochemical Expression Pattern of FGFR1, FGFR2, RIP5, and HIP2 in Developing and Postnatal Kidneys of Dab1−/− (yotari) Mice

“…Over the last couple of years, some genetic mutations responsible for structural kidney disease have been explored, including mutations in FGFRs [39][40][41][42]. As FGFR activation causes a pro-proliferative, anti-apoptotic, and pro-survival response [20,22,25], it is justifiable to speculate about the impaired cell response caused by Dab1 silencing. Our prior research revealed the CAKUT phenotype resulting in yotari [2].…”

“…In diabetes, the rising evidence highlights the protective implications of FGFR1 and endothelial FGFR1 [21]. It has been shown that FGFR1 increases the levels of renal protective microRNAs, which play a critical role in kidney development [22]. It is well known that some bioavailable peptides protect the kidneys by increasing FGFR1 expression or suppressing inflammatory cytokines [23][24][25].…”