Long noncoding RNA MIAT inhibits the progression of diabetic nephropathy and the activation of NF-κB pathway in high glucose-treated renal tubular epithelial cells by the miR-182-5p/GPRC5A axis

Abstract

Background Diabetic nephropathy (DN) is a common diabetic complication. Long noncoding RNAs (lncRNAs) have been identified as essential regulators in DN progression. This study is devoted to the research of lncRNA-myocardial infarction-associated transcript (MIAT) in DN. Methods DN cell model was established by high glucose (HG) treatment for human renal tubular epithelial cells (HK-2). Cell viability and colonizing capacity were analyzed by Cell Counting Kit-8 (CCK-8) and colony formation assay. Apoptosis was assessed via caspase-3 detection and flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used for evaluating inflammation. The protein determination was completed using western blot. MIAT, microRNA-182-5p (miR-182-5p), and G protein-coupled receptor class C group 5 member A (GPRC5A) levels were all examined via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Intergenic binding was verified using dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays. Results HG induced the inhibition of cell growth, but accelerated apoptosis and inflammation as well as the activation of nuclear factor kappa B (NF-κB) pathway. MIAT reestablishment prevented the HG-induced cell damages and NF-κB signal activation. Mechanistically, MIAT was proved as a miR-182-5p sponge and regulated the expression of GPRC5A that was a miR-182-5p target. The rescued experiments demonstrated that MIAT downregulation or miR-182-5p upregulation aggravated the HG-induced cell damages and activated the NF-κB pathway via the respective regulation of miR-182-5p or GPRC5A. Conclusion Taken together, MIAT functioned as an inhibitory factor in the pathogenesis to impede the development of DN and inactivate the NF-κB pathway via regulating the miR-182-5p/GPRC5A axis.

The Role of ncRNAs in Cardiac Infarction and Regeneration

“…In addition, inflammatory factors are significantly reduced by the silencing of MIAT throughout the activation of PI3K/Akt signaling pathway [ 223 ]. Additional evidence in this vein was reported in the study by Tan et al [ 41 ], in which a MIAT knockdown led to the reversal of cell proliferation, apoptosis, and inflammatory injury in miR-181a-5p-silenced or JAK2-overexpressing OGD-included CMs; further evidence was provided by Dong et al [ 224 ], who reported that MIAT sponges miR-182-5p and thereby regulates GPRC5A expression in vitro. Importantly, MIAT knockdown reduces myocardial injury caused by I/R treatment in vivo [ 41 ].…”

Screening and identification of key biomarkers in diabetic kidney disease and its complications: Evidence from bioinformatics and next generation sequencing data analysis

“…[697], IL18 [698], CYGB (cytoglobin) [636], EGF (epidermal growth factor) [699], TRPM2 [700], BANK1 [701], SORT1 [643], HSPG2 [645], NOX4 [702], MYH9 [703], TRPV4 [704], B4GALNT1 [705], LAG3 [706], CACNA1C [654], LRP5 [707], PIM1 [658], MDK (midkine) [708], CA2 [709], TRPC6 [710], CYP2D6 [711] and STAT4 [712] might be a biological target of type 1 diabetes mellitus. CCK (cholecystokinin) [713], IL33 [714], IRF4 [715], CXCL8 [716], MMP3 [717], DDIT4L [718], KL (klotho) [719], CXCL6 [87], CXCL1 [720], STC1 [721], PDK4 [722], RAB27B [723], CXCL5 [724], GPRC5A [725], TXNIP (thioredoxin interacting protein) [726], RAB3B [727], HSPA5 [728], DKK1 [93], NAMPT (nicotinamidephosphoribosyltransferase) [729], TNFAIP3 [730], GHR (growth hormone receptor) [731], ANXA1 [732], CD40 [733], KITLG (KIT ligand) [734], SMURF2 [735], NRG1 [684], GCLC (glutamate-cysteine ligase catalytic subunit) [685], NPHP1 [736], EPOR (erythropoietin receptor) [737], ADK (adenosine kinase) [738], SAA1…”

The role of long non‐coding RNAs in the development of diabetic kidney disease and the involved clinical application

“…120 By downregulating miR-182-5p and upregulating G protein-coupled receptor family C group 5 member A (GPRC5A), MIAT transfection of HK-2 cells counteracted HG-induced cell injury and NF-κB signalling pathway activation. 121 In conclusion, more research is required to determine the expression levels and functional roles of XIST and MIAT in different kidney cells.…”