The Interplay of NEAT1 and miR-339-5p Influences on Mesangial Gene Expression and Function in Various Diabetic-Associated Injury Models

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.

Reconstituted Extracellular Vesicles from Human Platelets Decrease Viral Myocarditis in Mice

“…Published role Reference miR-10a-5p Inhibits autoimmune T-cell responses [71] miR-19b-3p a) Increases innate immune response including TLR4 [72,73] miR-23b-3p Reduces cardiomyopathy by targeting/ reducing MyD88-induced NF𝜅B [74,75] miR-26a-5p Reduces fibrosis in lung, reduced in DCM patients and protects heart in animal model [76,77] miR-30a-5p Increased with CVB3 infection, protects against CVB3 myocarditis [78][79][80] miR-31-5p Targets CD40L and SAP to prevent activation of T helper cells [81] miR-99b-5p Inhibits NLRP3 inflammasome, inhibits PI3K/AKT/mTOR signaling [82,83] miR-125b-5p Associated with a number of cardiovascular diseases, but shown to inhibit IL-1𝛽 by targeting TRAF6/MAPK/NF𝜅B signaling [84][85][86][87] miR-143-3p Decreases TLR4, MyD88, and NF𝜅B and increases IL-10 [88] miR-145-5p Decreases TLR4 and PI3K/AKT/mTOR signaling [89,90] miR-148a-3p Inhibits IL-1𝛽 damaging effects and is inhibited by IL-1𝛽, inhibits NF-𝜅B during acute viral myocarditis [91,92] miR-148b-3p Increases proliferation of MSCs and Th2 responses that inhibit TLR4 [93,94] miR-152-3p Decreases PI3K/AKT signaling, inhibits mitochondrial autophagy [95,96] miR-186-5p Increases anti-viral beta-defensin-1 [97] miR-208b-3p Biomarker of sudden cardiac death, but fibroblasts treated with this miR when implanted in myocardial infarcts regenerated the heart and improved cardiac function [98,99] miR-339-5p Targets NEAT1 which regulates innate immune function [100,101] miR-345-5p Targets Drp1 and induces mitochondrial fission, decreases fibrosis by targeting HIF1a [77,102] miR-486-5p Increased with viral infections, but antiviral role…”

Emerging roles of the long non-coding RNA NEAT1 in gynecologic cancers

“…It has been confirmed that direct binding of NEAT1 to miR-27b-3p repressed diabetic nephropathy (Wang et al 2019a ). NEAT1 by interaction with miR-339-5p has been implicated in mesangial gene expression and functions in diverse diabetic-correlated injury models (Reichelt-Wurm et al 2022 ). A recent study on acute kidney injury (AKI) observed that high expression of Neat1-2 by suppressing miR-129-5p induced kidney injury and apoptosis (Ma et al 2022 ).…”