The Interplay of NEAT1 and miR-339-5p Influences on Mesangial Gene Expression and Function in Various
Simone Reichelt-Wurm1, Matthias Pregler1, Tobias Wirtz1
1Department of Nephrology, University Hospital Regensburg, 93053 Regensburg, Germany.
Abstract:
Mesangial cells (MCs), substantial cells for architecture and function of the glomerular tuft, take a key role in progression of diabetic kidney disease (DKD). Despite long standing researches and the need for novel therapies, the underlying regulatory mechanisms in MCs are elusive. This applies in particular to long non-coding RNAs (lncRNA) but also microRNAs (miRNAs). In this study, we investigated the expression of nuclear paraspeckle assembly transcript 1 (NEAT1), a highly conserved lncRNA, in several diabetes in-vitro models using human MCs. These cells were treated with high glucose, TGFβ, TNAα, thapsigargin, or tunicamycin. We analyzed the implication of NEAT1 silencing on mesangial cell migration, proliferation, and cell size as well as on mRNA and miRNA expression. Here, the miRNA hsa-miR-339-5p was not only identified as a potential interaction partner for NEAT1 but also for several coding genes. Furthermore, overexpression of hsa-miR-339-5p leads to a MC phenotype comparable to a NEAT1 knockdown. In-silico analyses also underline a relevant role of NEAT1 and hsa-miR-339-5p in mesangial physiology, especially in the context of DKD.
Insights
The long non-coding RNA NEAT1 and microRNA hsa-miR-339-5p play crucial roles in regulating mesangial cell behavior, offering potential therapeutic targets for diabetic kidney disease (DKD).
Area of Science:
- Nephrology
- Molecular Biology
- Genetics
Background:
- Diabetic kidney disease (DKD) progression involves mesangial cell (MC) dysfunction.
- Regulatory mechanisms, particularly involving long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), in MCs remain poorly understood.
- Novel therapeutic targets for DKD are urgently needed.
Purpose of the Study:
- To investigate the role of the lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in human MCs under diabetic conditions.
- To analyze the impact of NEAT1 modulation on MC phenotype and gene expression.
- To identify potential interactions between NEAT1, miRNAs, and coding genes relevant to DKD.
Main Methods:
- Human MCs were cultured and treated with high glucose and other stressors (TGFβ, TNAα, thapsigargin, tunicamycin) to model diabetes.
- NEAT1 expression was investigated, and NEAT1 silencing was performed.
- MC migration, proliferation, and cell size were assessed.
- mRNA and miRNA expression profiling was conducted.
- In-silico analyses were employed to predict interactions.
Main Results:
- NEAT1 expression was examined in MCs under various diabetic stress conditions.
- NEAT1 silencing significantly altered MC migration, proliferation, and cell size.
- The miRNA hsa-miR-339-5p was identified as a potential interaction partner for NEAT1 and coding genes.
- Overexpression of hsa-miR-339-5p mimicked the phenotypic changes observed after NEAT1 knockdown.
- In-silico analyses supported the involvement of NEAT1 and hsa-miR-339-5p in MC physiology and DKD.
Conclusions:
- NEAT1 is implicated in regulating mesangial cell behavior relevant to diabetic kidney disease.
- The lncRNA NEAT1 and miRNA hsa-miR-339-5p represent potential therapeutic targets for DKD.
- Further research into the NEAT1/hsa-miR-339-5p axis could elucidate DKD pathogenesis and inform treatment strategies.
