Table 2.

LncRNAs currently implicated in diabetes and other disease-associated models.

lncRNA	Cell/Tissue Type(s)	Reported Function(s)	Disease Model
PVT1	• Humanmesangial cells	• Upregulated by glucose treatment in mesangial cells • PVT1 knockdown can significantly reduce the levels of major ECM proteins (FN and COL4A1)	• DN [146]
MALAT1	• Mice kidney tissues • Mouse podocytes • Mice and rat cardiac tissues • HRECs • Mice retinal tissues • RF/6A cells • Aqueous and vitreous humors	• MALAT1 levels are increased in the kidney cortices of STZ-induced diabetic mice [147] • MALAT1 regulates diabetes-induced inflammatory gene expressions in the heart and kidneys [148,149] • MALAT1 is upregulated in HG-treated RF/6A cells, aqueous humor samples and in fibrovascular membranes of diabetic patients [167] • MALAT1 has a pathogenetic role in the heart [165,166] • MALAT1 can regulate inflammation through its association with other epigenetic mechanisms in DR [168]	• DN [147,148,149] • DR [167,168] • DCM [148,165,166]
GM4419	• Mouse mesangial cells (MMCs)	• Upregulated in MMCs following high glucose culture • Knockdown of GM4419 inhibits the glucose-induced expressions of pro-inflammatory cytokines and renal fibrosis markers • GM4419 can regulate NF-κB signalling	• DN [150]
GM5524	• Mice kidney tissues • Mouse podocytes	• Expressions are significantly upregulated in DN • May regulate podocytes apoptosis and autophagy during DN	• DN [151]
GM15645	• Mice kidney tissues • Mouse podocytes	• Downregulated in DN • Similar to GM5524, GM15645 may also regulate podocytes apoptosis and autophagy during DN	• DN [151]
ANRIL	• Human retinal endothelial cells (HRECs) • Mice retinal tissues • Mice kidney and cardiac tissues	• High glucose and diabetic conditions upregulate ANRIL expressions [81,154] • ANRIL can regulate VEGF and ECM expressions through several epigenetic mechanisms (i.e., p300 and PRC2) [81,154]	• DN [154] • DR [81] • DCM [154]
NR_033515	• Human blood • HEK293-T • MMCs	• Significantly increased in the serum of DN patients • Overexpression of NR_033515 can accelerate TGF-β1-induced EMT • Promotes cell proliferation and fibrogenesis in high glucose conditions	• DN [152]
Erbb4-IR	• Mice kidney tissues • Mouse embryonic fibroblasts • MMCs • Mouse tubular epithelial cells	• Significantly upregulated in the kidneys of diabetic mice • A Smad3-dependent lncRNA that promotes renal fibrosis in type 2 DN • Can negatively regulate miR-29b • Kidney-specific silencing of Erbb4-IR shown to prevent renal injury in diabetic mice	• DN [153]
ASncmtRNA-2	• Mice kidney tissues • Human mesangial cells	• Expressions are significantly heightened in diabetic mice kidneys and mesangial cells treated with high glucose • May promote glomerular fibrosis in DN	• DN [155]
Tug1	• Mice kidney tissues • MMCs	• Suppresses the proliferation of mesangial cells and decreases the expression of ECM-associated proteins in DN • Functions as an endogenous sponge of miR-377, which directly targets PPARγ	• DN [156]
NONMMUT022554	• Mice cardiac tissues	• Upregulated in cardiac fibrosis and positively correlated with 6 upregulated genes involved in ECM–receptor interactions and the PI3K–Akt signalling pathway	• Cardiac fibrosis/MI [160]
PFL (NONMMUT022555)	• Mice cardiac tissues • Mice cardiac fibroblasts and cardiomyocytes	• Upregulated in the hearts of MI mice • Knockdown of PFL can attenuate cardiac interstitial fibrosis and improve cardiac function • Overexpression of PFL promotes proliferation, fibroblast-myofibroblast transition, and mice cardiac fibroblasts • Acts as a competitive endogenous RNA of let-7d	• Cardiac fibrosis/MI [161]
MIAT	• Mice cardiac tissues • Mouse cardiac fibroblasts	• Significantly upregulated in the infarcted myocardium of mice • Knockdown of MIAT reduces cardiac fibrosis and improves cardiac function • Functions as a sponge of miR-24 in cardiac fibroblasts	• Cardiac fibrosis/MI [162]
Wisper	• Mice and human cardiac tissues • Mouse cardiac fibroblasts and cardiomyocytes • Human fibroblasts	• Expression of Wisper is strongly correlated with cardiac fibrosis in both animal and human heart tissues • Wisper knockdown affects cardiac fibroblast survival, migration, and proliferation • In vivo depletion of Wisper inhibits cardiac fibrosis and improves function	• Cardiac fibrosis/MI [163]
Meg3	• Mice cardiac tissues • Mouse cardiac fibroblasts	• Strongly expressed in adult cardiac fibroblasts • Regulates the production of MMP-2 in vitro • In vivo inhibition of Meg3 after transverse aortic constriction decreases cardiac fibrosis and improves diastolic function	• Cardiac fibrosis [164]
H19	• HRECs • Mice retinal tissues • Human vitreous humors	• Downregulated in HG-treated endothelial cells and in the vitreous humors of diabetic patients • Capable of regulating EndMT in vitro and in vivo	• DR [170]
Lnc-MGC	• Mice kidney tissues • Mouse and human mesangial cells • Human renal biopsies	• Elevated levels of lnc-MGC present in the kidneys during diabetes • Host to a megacluster of miRNAs • CHOP (an ER-stress transcription factor) regulates lnc-MGC expressions • Inhibition of lnc-MGC results in reduced cluster miRNAs, ECM accumulation, and glomerular hypertrophy	• DN [158]

DN = diabetic nephropathy; DR = diabetic retinopathy; DCM = diabetic cardiomyopathy; MI = myocardial infarction; ECM = extracellular matrix; STZ = streptozotocin; PPARγ = peroxisome proliferator-activated receptor gamma; MMP-2 = matrix metalloproteinase-2; EMT = epithelial–mesenchymal transition; EndMT = endothelial–mesenchymal transition; HG = high glucose.