The Role of MicroRNA in the Pathogenesis of Diabetic Nephropathy
Abstract
:1. Introduction
2. The Role of MicroRNA in the Pathogenesis of Diabetic Nephropathy
2.1. miRs Involved in Modulating TGF-β Signaling
2.2. miR Affecting Collagen Expression
2.3. miR Regulating the PTEN-Dependent Pathways
2.4. miR Affecting Other Pathways Involved in the Pathogenesis of the Disease
3. miRs That Elicit Protective Properties in Diabetic Nephropathy
4. miRs as Therapeutic Targets in Treatment and Prevention of DN
5. Select miR as Biomarkers of the Disease
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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miRNA | Up/Downregulation | Target Protein or Pathway | Outcome | Model | Reference |
---|---|---|---|---|---|
miR-192 | Up | ZEB1/SIP1 | TGF- β -induced increased COL1α1 and COL1α2 expression | Mouse | [47] |
miR-192 | Up | ZEB1/2 | Increased TGF-β signaling, increased fibrosis | Mouse | [46] |
miR-216a | Up | PTEN, YBX1 | TGF-β-induced collagen expression | Mouse mesangial cells | [68] |
miR-217 | Up | PTEN | Increases mesangial cell survival | Mouse mesangial cells | [69] |
miR-200b/c | Up | ZEB1 | Mediates TGF-β1 autoregulation, increases COL1α2 and COL4α1 expression | Mouse | [46] |
miR-200b/c | Up | FOG2, TGF-β | Akt kinase activation, glomerular mesangial hypertrophy | Mouse | [48] |
miR-21 | Up | PTEN, PRAS40, TORC1 | Renal hypertrophy through Akt/TORC1 pathway | Human mesangial cells | [70] |
miR-21 | Up | SMAD7 | activation of the TGF-β and NF-κB signaling pathways | Mouse | [51] |
miR-21 | Up | SirT1 | TIMP3 downregulation | Mouse | [76] |
miR-21 | Up | MMP9/TIMP1 | Increased collagen and FN expression | Mouse | [56] |
miR-21 | Up | PTEN-SMAD7 | Regulation of renal tubular ECM via Smad3/Akt pathway | Mouse | [71] |
miR-377 | Up | PAK1, SOD | Increased FN production | Mouse | [57] |
miR-195 | Up | Bcl2 | Promotes apoptosis via enhanced caspase cascade | Mouse | [78] |
miR-215 | Up | CTNNBIP1 | Promotes TGF-β driven mesangial cell phenotypic transition | Mesangial cells | [52] |
miR-124 | Up | Integrin α3β1 | Downregulation of podocyte α3 and β1 that leads to adhesion damage under mechanical stress | Human podocytes | [84] |
miR-29c | Up | Spry1 | Activation of Rho kinase, albuminuria, mesangial matrix accumulation | Mouse podocytes | [58] |
miR-29c | Up | Tristetrapolin | Promotes inflammatory response via increase of TNF-α and IL-6 | Human plasma and urine | [80] |
miR-1207-5p | Up | PMEPA1, G6PD, PDPK1 | ECM accumulation through TGF-β | Human podocytes | [49] |
miR-135a | Up | TRPC1 | Increases FN and collagen synthesis | Human serum and kidney tissue, mouse | [62] |
miR-200a | Down | TGF-β2 | Increased FN and collagen synthesis | Rat tubular epithelial cells | [53] |
miR-141 | Down | TGF-β2 | Increased FN and collagen synthesis | Rat tubular epithelial cells | [53] |
miR-29 | Down | Collagen I and collagen IV | Increased collagen production and fibrosis | Rat tubular epithelial cells, mesangial cells, podocytes | [60] |
miR-29a | Down | COL4α1, COL4α2 | Excess collagen deposition | Human tubular cel line | [61] |
miR-29a | Down | HDAC4 | Podocyte protein deacetylation and degradation as well as renal dysfunction | Mouse | [85] |
miR-29b | Down | TGF-β/Smad3 | Upregulation of collagen matrix in mesangial cells | Mouse | [54] |
miR-451 | Down | YWHAZ | Upregulation of p38 MAPK signaling, mesangial proliferation | Mouse mesangial cells | [81] |
miR-25 | Down | NOX4 | Increased NOX4 expression | Rat | [82] |
miR-93 | Down | VEGF-A | Increased fibrosis | Mouse, endothelial cells, podocytes | [86] |
miR-22 | Up | PTEN | Suppression of autophagic flux and induction of Col IV and α-SMA expression | Rat renal cells | [73] |
miR-27a | Up | PPARγ | Increased ECM accumulation, proteinuria | Rat | [87] |
miR-92b-3p | Up | SMAD7 | Increased TGF-β signaling and renal fibrosis | Rat | [83] |
miR-141-3p | Up | PTEN | Increased renal fibrosis through miR-141-3p/PTEN/Akt/mTOR pathway | Rat | [74] |
miR-181a | Up | Deptor | Leads to TGFβ-induced mesangial cell hypertrophy and matrix protein FN expression | Rat mesangial cells | [88] |
miR-184 | Up | LPP3 | Tubulointerstitial fibrosis and albuminuria | Rat | [89] |
miR-214 | Up | PTEN | Cell hypertrophy and expression of the matrix protein FN | Mouse | [72] |
miR-218 | Up | HO-1 | Acceleration of podocyte apoptosis through directly downregulating HO-1 and facilitating p38-MAPK activation | Mouse podocytes | [79] |
miR-23c | Down | MALAT1 | Contributes to hyperglycemia-induced cell pyroptosis | Renal tubular epithelial cells | [90] |
miR-25 | Down | PTEN/Akt | Oxidative stress and apoptosis in renal tubular epithelial cells | Renal biopsy tissue | [75] |
miR-30c | Down | CTGF | Upregulation of CTFG results in renal fibrosis | Human kidney tubular epithelial cells | [91] |
miR-130b | Down | Snail | Deregulated E-CADHERIN, VIMENTIN, COLLAGEN IV and α-smooth muscle actin (α-SMA), key mediators of thus affecting epithelial-to-mesenchymal transition | Rat | [92] |
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Szostak, J.; Gorący, A.; Durys, D.; Dec, P.; Modrzejewski, A.; Pawlik, A. The Role of MicroRNA in the Pathogenesis of Diabetic Nephropathy. Int. J. Mol. Sci. 2023, 24, 6214. https://doi.org/10.3390/ijms24076214
Szostak J, Gorący A, Durys D, Dec P, Modrzejewski A, Pawlik A. The Role of MicroRNA in the Pathogenesis of Diabetic Nephropathy. International Journal of Molecular Sciences. 2023; 24(7):6214. https://doi.org/10.3390/ijms24076214
Chicago/Turabian StyleSzostak, Joanna, Anna Gorący, Damian Durys, Paweł Dec, Andrzej Modrzejewski, and Andrzej Pawlik. 2023. "The Role of MicroRNA in the Pathogenesis of Diabetic Nephropathy" International Journal of Molecular Sciences 24, no. 7: 6214. https://doi.org/10.3390/ijms24076214