Table 1.
List of the reported noncoding RNAs in Diabetic Nephropathy.
| Noncoding RNA | Expression | Sample types | Origin/population | Molecular target | Function—pathogenesis |
|---|---|---|---|---|---|
| MicroRNAs | |||||
| miR-15b | Up | Urine exosome | T2DM patients—albuminuria and non-albuminuria (Eissa et al., 2016a) | NA | DN changes |
| Podocyte cells | Mouse cell line (Fu et al., 2019) | TNF α, IGFBP3, SEMA3A, IL1B, IL6 | |||
| miR-20b | Up | Podocyte cells, HEK293T cells | Mouse and human cell line (Wang et al., 2017) | SIRT7 | Podocyte cells apoptosis |
| miR-21 | Up | renal cortical tissue | db/db DN mice (strain: C57BL/6JLepr) (Zhang et al., 2009) | PTEN, AKT, PIK3CA | Renal cell proliferation and hypertrophy |
| Renal tissue, podocyte cells, HEK293T cells | DN patients, DN STZ Sprague-Dawley rats, mouse cell line, and human cell line (Chen et al., 2018) | IL1B, TNF α, TIMP3 | Podocyte cells inflammatory and apoptosis | ||
| Renal tissue, podocyte cells, HEK293T cells | C57BL/6J < sp > Lepr</sp> (Wang et al., 2019a) | FOXO1, MAP1LC3A, KHDRBS1, P62 | Podocyte cells apoptosis and autophagy inhibition | ||
| miR-22 | Up | Renal tissue, NRK-52E cells | STZ Sprague-Dawley rats (Zhang et al., 2018) | PTEN, COL4, α-SMN1 | Inhibit autophagy process and renal fibrosis |
| miR-27a | Up | Kidney tubular epithelial cells, renal tissues | T2DM patients, rat cell line and diabetic Sprague Dawley rats (Hou et al., 2016) | PPARG, Tgfb1, Smad3, Ccn2, Fn1, COL1 | Renal fibrosis |
| NRK-52E, HK-2, HBZY-1 cell lines, renal tissues, | db/db diabetic and cell lines (Song et al., 2018) | Gabpa, Itln1 | The pro-inflammatory response, oxidative stress | ||
| podocyte cells | T2DM patients with DN, murine cell line and diabetic rats (Zhou et al., 2017) | Pparg, Ctnnbip1, Snai1, Acta2 | Podocyte cells injury and apoptosis | ||
| miR-34a | Up | Urine exosomes | T2DM patients—albuminuria and non-albuminuria (Eissa et al., 2016a) | NA | DN changes |
| miR-130a | Up | Urine exosomes, renal tissues, human mesangial cells | T1DM patients with DN, DN mice, and human cell line (Barutta et al., 2013) | NA | DN changes |
| miR-130b | Up | Renal tissues, mesangial cells | DN patients and cell line (Ma et al., 2019) | TGFB1, COL1, COLIV, FN, t‐Smad2/3, p‐Smad2/3, and SMAD4 | Renal fibrosis, and extracellular matrix accumulation |
| miR-133b | Up | Urine exosomes | T2DM patients—albuminuria and non-albuminuria (Eissa et al., 2016b) | TGFB1 | DN changes |
| Renal cortex, human proximal tubule cell line, HEK293T cells | OLETF mice and human cell line (Sun et al., 2018c) | CDH1, TGFB1, COL1, FN, ACTA2, SIRT1 | Epithelial-mesenchymal transition, and renal fibrosis | ||
| miR-134-5p | Up | Renal tissues, podocyte cells | Db/db mice (Qian et al., 2018) | BCL2 | Podocytes apoptosis |
| miR-135a | Up | Serum, renal tissues, mesangial cells, HEK293T cells | DN patients, healthy control, and db/db mice, cell line (He et al., 2014) | TRPC1, FN, COL1, TGFB1, PCNA, CCND1, P21, CDH, VIM | Mesangial cells proliferation, increase extracellular matrix proteins, and renal fibrosis |
| miR-141 | Up | Mesangial cells | Human cell line (Li et al., 2018b) | IRS2 | Renal hypertrophy, inflammation, and cell apoptosis |
| miR-145 | Up | Urine exosomes, renal tissues, human mesangial cells | T1DM patients with DN, DN mice, and human cell line, (Barutta et al., 2013) | STAT1, TGFB1 | Mesangial cells damage |
| miR-155-5p | Up | Proximal tubular cells | Human Cell line (Wang et al., 2018e) | SIRT1, LC3 II, ATG5 | Autophagy |
| miR-181a | Up | Plasma | DN patients (Bijkerk et al., 2015) | NA | Microvascular damage |
| miR-181b | Up | Glomerular mesangial cells, renal biopsy | DN patients (Zhu et al., 2019) | TIMP3 | Mesangial cells apoptosis |
| miR-182-5p | Up | Renal biopsy, podocyte cells | DN patients and cell line (Ming et al., 2019) | CD2AP, FOXO1, BCL2 | Podocyte cells injury and apoptosis |
| miR-192 | Up | Renal cortical tissues, mesangial cells | db/db mice (Kato et al., 2009) | Tgfb1, Akt, Pten, E box | Glomerular hypertrophy, mesangial cells expansion, Renal fibrosis, extracellular matrix accumulation, and tubular damage Glomerular hypertrophy and mesangial cells expansion |
| Urine extracellular vesicles, renal tubular epithelial cells, mesangial cells, | Albuminuria patients and human cell line (Jia et al., 2016) | TGFB1 | Tubular and mesangial cells damage | ||
| Renal biopsy | DN patients (Krupa et al., 2010) | TGFB1, ZEB1, CDH1 | Tubulointerstitial fibrosis | ||
| miR-194 | Up | Urine extracellular vesicles, human renal tubular epithelial cells, human mesangial cells | DN patients with T2DM and human cell line (Jia et al., 2016) | AKT, TRAF6 | Tubular and mesangial cells damage |
| miR-195 | Up | Plasma and urine | CKD patients (Sayilar et al., 2016) | NA | DN changes |
| miR-199b | Up | Renal cortex, human proximal tubular epithelial cells | OLETF mice and human cell line (Sun et al., 2018a) | CDH1, TGFB1, COL1, FN, ACTA2, SIRT1 | Epithelial-mesenchymal transition, and renal fibrosis |
| miR-200 | Up | Renal cortex tissues, mesangial cells | db/db mice (Park et al., 2013) | Fog2, Pi3k, Tgfb1 | Glomerular mesangial hypertrophy |
| miR-212 | Up | Renal, plasma | Sprague-Dawley rats (Eskildsen et al., 2013) | Angiotensin, MAPK3 | Hypertension in renal |
| miR-215 | Up | Urine extracellular vesicles, renal tubular epithelial cells, mesangial cells | Albuminuria patients and human cell line (Jia et al., 2016) | TGFB1 | Tubular and mesangial cells damage |
| miR-216a | Up | Renal cortex tissues, mesangial cells | db/db mice (Kato et al., 2009) | Tgfb, Akt, Pten, Zeb1 | Glomerular hypertrophy and mesangial cells expansion |
| miR-217 | Up | Renal cortex tissues, mesangial cells | db/db mice (Kato et al., 2009) | Tgfb, Akt, Pten, Zeb1 | Glomerular hypertrophy and mesangial cells expansion |
| miR-320 | Up | Renal cortex tissues, podocyte cells | Db/db mice (He et al., 2019) | Mafb | Podocyte cells injury and apoptosis |
| miR-324-3p | Up | Glomerular cells, tubular cells | Munich Wistar Fromter mice (Macconi et al., 2012) | Angiotensin, Ac-SDKP, Prep | Renal fibrosis |
| miR-337 | Up | Renal tissues, mesangial cells | DN mice and human cell line (Wang et al., 2008) | TGFB | Mesangial cells expansion, and renal toxicity and fibrosis |
| miR-342 | Up | Urine exosomes | T2DM patients—albuminuria and non-albuminuria (Eissa et al., 2016b) | TGFB1 | DN changes |
| miR-370 | Up | Renal tissues, mesangial cells | DN mice (Yu et al., 2019) | Cnpy1 | Mesangial cells proliferation and extracellular matrix accumulation |
| miR-377 | Up | Renal tissues, mesangial cells | DN mice and human cell line (Wang et al., 2008) | FN, PAK1, SOD1, SOD2, TGFB | Renal toxicity and fibrosis |
| Renal cortex, mesangial cells | T2DM db/db mice and mice cell line (Kato et al., 2016) | Tgfb1, Akt, Erk, Chop, Edem3 | Endoplasmic reticulum stress, and glomerular extracellular matrix and hypertrophy | ||
| miR-379 | Up | Renal tissues, mesangial cells | db/db mice and mouse cell line (Kato et al., 2016) | Tgfb1, Akt, Erk, Chop, Edem3 | Renal toxicity and fibrosis, endoplasmic reticulum stress, extracellular matrix accumulation, and podocyte cells injury |
| miR-382 | Up | Renal tissue, mesangial cells | STZ mice (Wang et al., 2018c) | Foxo1 | Renal hypertrophy and extracellular matrix accumulation |
| miR-4449 | Up | Serum exosomes | DN patients (Kim et al., 2019) | NA | Angiogenesis |
| miR-451 | Up | Plasma and urine | CKD patients (Sayilar et al., 2016) | NA | DN changes |
| Renal tissues, primary mouse mesangial cells | DN mice, and cell line (Zhang et al., 2012), | Ywhab, P38 Mapk | Renal fibrosis and glomerular cells proliferation | ||
| miR-494 | Up | Renal tissues, mesangial cells | db/db mice and cell line (Kato et al., 2016) | Tgfb1, Akt, Erk, Chop | Renal toxicity and fibrosis |
| miR-495 | Up | Renal tissues, mesangial cells | db/db mice and cell line (Kato et al., 2016) | Tgfb1, Akt, Erk, Chop | Renal toxicity and fibrosis |
| Urine | T1DM patients with DN (Christos et al., 2015) | NA | DN changes | ||
| miR-503 | Up | Renal tissues, podocyte cells | STZ mice (Zha et al., 2019) | E2f3 | Podocyte cells injury and apoptosis |
| miR-636 | Up | Urine exosome | T2DM patients—albuminuria and non-albuminuria (Eissa et al., 2016a) | NA | DN changes |
| miR-770-5p | Up | Podocyte cells | Mice cell line (Zhang et al., 2019) | Triap1 | Podocyte cells apoptosis and cells death |
| miR-181a | Down | Renal tissue | Hypertensive and normotensive patients (Marques et al., 2011) | AIFM1, APOE, RENIN | Hypertension in renal |
| miR-25 | Down | Serum, renal tissue, and HK-2 cells | DN patients and human cell line (Li et al., 2017a) | PTEN, AKT | Renal tubular epithelial cell injury and apoptosis, mesangial cells injury, and glomerular hypertrophy |
| Renal tissue | STZ Sprague-Dawley rats (Fu et al., 2010) | NOX4 | |||
| Glomeruli, mesangial cell | STZ mice and cell line (Oh et al., 2016) | p-MeCP2, Hipk2, Tgfb | Oxidative stress | ||
| miR-26a | Down | Renal biopsy, STZ mice, and human podocyte cells | DN patients, STZ mice, and human cell (Koga et al., 2015) | TGFB, CTGF, SMAD, CTDSP2, CTDSPL | Extracellular matrix accumulation |
| miR-29a | Down | Glomeruli, podocyte cells | STZ mice (Lin et al., 2014) | Nephrin | Podocyte cell apoptosis |
| Mesangial cells | Mice and cell line (Tung et al., 2019) | Cb1r, Pparg | Renal hypertrophy | ||
| miR-30 | Down | Urine exosomes | T2DM patients—albuminuria and non-albuminuria (Eissa et al., 2016b) | NA | DN changes |
| miR-93 | Down | Renal microvascular endothelial cells, podocyte cells | Mice cell line and diabetes db/db mice (Long et al., 2010) | Vegfa, Mcm7 | Podocyte cells damage |
| Podocyte cells, renal tissues | Mice cell line and Cg-Dock7m+/+Leprdb/J mice (Badal et al., 2016) | Msk2 | |||
| Renal tissue, human renal tubular cells | DN patients and human cell line (Ma et al., 2018) | ORAI1, TGFB1 | Renal fibrosis and endothelial mesenchymal transition | ||
| miR-155 | Down | Urine exosomes, blood, renal tissues | DN patients and C57BL6/J mice (Barutta et al., 2013) | NA | Podocyte cells injury |
| miR-205 | Down | Renal tubules epithelial cells | Human cell line (Muratsu-Ikeda et al., 2012) | EGLN2, VEGF GLUT1, HIF-1α | Renal injury |
| miR-214 | Down | Renal, human renal proximal tubular epithelial cells | DN mice and human cell line (Yang et al., 2019) | UCP2 | Oxidative stress |
| miR-374a | Down | Renal biopsy, human proximal tubular epithelial cells | DN patients and human cell line (Yang et al., 2018b) | CCL2 | Induce inflammatory response |
| miR-423-5p | Down | Renal biopsy, podocyte cell | DN patients and mice cell line (Xu et al., 2018) | NOX4 | Oxidative stress and podocyte cells death |
| miR-424 | Up | Urine exosomes, renal tissues, human mesangial cells | T1DM patients with DN, DN mice, and human cell line, (Barutta et al., 2013) | NA | DN changes |
| miR-455-3p | Down | Mesangial cells, proximal tubular epithelial cells | Human cell line (Wu et al., 2018) | ROCK2 | Inflammation and fibrosis |
| miR-574-3p | Down | Plasma | DN patients (Bijkerk et al., 2015) | ANGPT2/ANGPT1, IGF1 | Effects renal function (eGFR and creatinine) |
| miR-663 | Down | Renal tissue | Hypertensive and normotensive patients (Marques et al., 2011) | AIFM1, APOE, RENIN | Hypertension in renal |
| miR-874 | Down | Renal cortex | STZ mice (Yao et al., 2018) |
TLR4, IL6, IL1B,
TNFA |
Podocyte cells proliferation and apoptosis |
| Let-7a-5p | Down | Renal tissue, mesangial cells | db/db mice and cell line (Wang et al., 2019c) | HMGA2 | Renal hypertrophy and apoptosis |
| Long noncoding RNAs | |||||
| ERBB4-IR | Up | Renal tissue | C57BL/6J mice (Zhou et al., 2014) | Smad3, Tgfb | Renal fibrosis |
| Renal cortex, mesangial cells, tubular epithelial cells | db/db mice and mice cell (Sun et al., 2018b) (Sun et al., 2018b) | Smad3, Tgfb1, miR-29b | |||
| GAS5 | Up | Human renal tubular epithelial cell | Human cell line (Lv et al., 2019) | miR-27a, P53, CASP3, BNIP3 | Renal tubular epithelial cells apoptosis |
| Gm4419 | Up | High glucose mesangial cells | Mice cells (Yi et al., 2017) | Nfkb | Renal inflammation and fibrosis. |
| GM5524 | Up | Renal tissues, podocyte cells | db/db mice (Feng et al., 2018) | CASP3, BAX, LC3I, LC3II Atg5, Atg7, Bcl2 | Podocyte cells apoptosis and cells autophagy |
| GM6135 | Up | Mesangial cells | db/db mice (Ji et al., 2019) | TLR4, miR‐203 | Mesangial cells proliferation and apoptosis |
| LncRNA CJ241444-miR-192 | Up | Renal cortical tissues, mesangial cells | Obese type 2 diabetic db/db mice and mouse cells (Kato et al., 2013) | Tgfb, Akt, Col1a2, Col4A1, Smad, Ets1, miR-192 | Mesangial cells fibrosis |
| Lnc-MGC | Up | Renal tissue, mesangial cells | STZ mice and human cell (Kato et al., 2016) | TGFB1, SMAD, CHOP | Renal toxicity and fibrosis, glomerular hypertrophy, extracellular matrix accumulation, and podocyte cells injury |
| LncRNA NR_033515 | Up | Serum, HEK293 T cells,mesangial cells | DN patients and mouse cell (Gao et al., 2018) | HAVCR1, PCNA, CCND1TGFB1, P38, ASK1, FN, ACTA2, CDH, VIM, miR-743b-5p | EMT and cell proliferation |
| Metastasis associated lung adenocarcinoma transcript 1 (MALAT-1) | Up | Umbilical vein endothelial cells, STZ mice | Human cell line and mice (Puthanveetil et al., 2015) | SAA3, TNF-α, IL-6 | Renal inflammation and fibrosis Microvascular inflammation |
| Podocyte cells, HEK‐293 cells | Human, C57BL/6 mice, cell line (Hu et al., 2017) | CTNNBIP1, SRSF1 | Podocyte cells damage | ||
| Renal tissues, proximal tubular epithelial cells | Sprague Dawley rats and human cell line (Li et al., 2017b) | miR-23c, ELAVL1, NLRP3 | Renal tubular epithelial cell pyroptosis | ||
| Serum | ESRD patients with diabetes (Fawzy et al., 2018) | miR-499a | DN changes | ||
| NEAT1 | Up | Renal tissues | Diabetic mice (Huang et al., 2019) | Akt, Mtor, Tgfb1, Fn, ColIv | Mesangial cell proliferation and fibrosis |
| Renal tissues | Sprague–Dawley rats (Wang et al., 2018d) | Zeb1, miR‐27b‐3p, Ask1, fibronectin, Tgfb1 | |||
| Plasmacytoma variant translocation (PVT1) | Up | Blood | Gila River Indian Community with T2DM and DN T1DM patients with DN (Hanson et al., 2007) | NA | DN changes |
| Blood, human primary renal cell | Pima Indians with T1DM and T2DM, and human cell line | NA | |||
| Mesangial cells | Human cell line (Alvarez and DiStefano, 2011) | FN1, COL4A1, SERPINE1, TGFB1 | Extracellular matrix accumulation and mesangial cells fibrosis | ||
| CASC2 | Down | Serum, renal tissue | DN patients (Wang et al., 2018a) | NA | Podocyte cells deaths |
| Serum, podocyte cells | DN patients and mouse (Yang et al., 2018a) | JNK1 | |||
| CYP4B1-PS1-001 | Down | Mesangial cells, renal cortex | db/db mice (Wang et al., 2018b) | Ncl | Renal proliferation and fibrosis |
| renal tissue, mesangial cells, HEK293T | C57BL/KsJ db/db mice, and human and mouse cell line (Wang et al., 2016a) | PCNA, CCND1, FN, COLI | Mesangial cells proliferation and fibrosis | ||
| ENSMUST00000147869 | Down | Renal cortex | db/db and db/m mice (Wang et al., 2016b) | Cyp4a12a | Mesangial cells proliferation and fibrosis |
| GM15645 | Down | Renal tissue, podocyte cells | db/db mice (Feng et al., 2018) | CASP3, BAX, LC3I, LC3II Atg5, Atg7, Bcl2 | Podocyte cells apoptosis and cells autophagy |
| LINC01619 | Down | Renal biopsy, cortex, podocyte cell | T2DM patients, and STZ Sprague Dawley rats (Bai et al., 2018) | FOXO1, ROS, CHOP, GRP78, miR-27a | Podocyte cells injury and apoptosis and endoplasmic reticulum stress |
| LncRNA 1700020I14Rik | Down | Renal tissue, mesangial cells | db/db and db/m mice (Li et al., 2018a) | Sirt1, Hif1a, Col4, Fn, Tgfb1, miR-34a-5p | Mesangial cells proliferation and fibrosis |
| lncRNA RIAN | Down | NIH3T3 cells and renal tissue | Mice and cell line (Bijkerk et al., 2019) | Acta2, Col1a1, Smad2, Smad3, miR-150 | Myofibroblast formation |
| Taurine up-regulated 1 (TUG-1) | Down | Renal cortex, mesangial, podocytes cells | db/db and db/m mice and cell line (Long et al., 2016) | Ppargc1a | Podocyte cells death and extracellular matrix accumulation Reduce glomerular filtration rates and podocyte cells apoptosis |
| Renal cortex, mesangial cells | C57BL/KsJ-db/db mice and mice cell line (Duan et al., 2017) | miR-377, Pparg, Serpine1, Tgfb1, Fn, Col Iv | Extracellular matrix accumulation of mesangial cells | ||
| Renal tissues, podocyte cells | Sprague Dawley rats and mice cell line (Lei et al., 2018) | Traf5 | Podocyte cells apoptosis | ||
| Renal biopsy, podocyte cells | DN patients and human cell line (Shen et al., 2019) | PGC‐1α, CHOP | Podocyte cells apoptosis and endoplasmic reticulum stress | ||
| Myocardial infarction associated transcript (MIAT) | Down | Proximal convoluted tubule, proximal tubular epithelial cell line (HK-2) | STZ Wistar rats and cell line (Zhou et al., 2015) | Nrf2, Acta2, Smad2/3, Col1a1 | Renal cell apoptosis and fibrosis |
| Circular noncoding RNAs | |||||
| circRNA_15698 | Up | Renal cortex, mesangial cells | C57BL/KsJ‐db/db mice (Hu et al., 2019) | Tgfb1, Col1a1, Col4a1 and Fn, miR‐185 | Renal fibrosis |