Table 4.
TGF-β-related dysregulation of miRNAs in DKD
| miRNA | In vivo detection | Supposed mechanisms | |
|---|---|---|---|
| let-7d | TGF-β1 decreases let-7d in NRK-52E cells -> Col I ↑, E-cadherin ↓ | [130] | |
| let-7d | ↓ in glomeruli of STZ-treated mice | TGF-β1 decreases let-7d in mouse mesangial cells -> TGF-R1 ↑ | [131] |
| miR-34a-5p | ↑ in db/db mice | Upregulation of miR-34a-5p -> SIRT1 ↓ -> TGF-β1 ↑, fibronectin ↑ -> kidney fibrosis | [132] |
| miR-130b | ↓ in glomeruli of STZ-treated mice | TGF-β1 decreases miR-130b in mouse mesangial cells -> TGF-R1 ↑, Col4A1 ↑, Col12A1 ↑, CTGF ↑, PAI-1 ↑ | [131] |
| miR-143/145 | ↑ in glomeruli of db/db mice | TGF-β1 -> SMAD signaling or mTOR -> miR-143/145 ↑ in human podocytes -> WT-1 ↓, Zonula-1 ↓, Col I ↑, α-SMA ↑ | [133] |
| miR-154-5p | ↑ in glomeruli of STZ and high-fat diet rats | miR-154-5p ↑ in rat mesangial cells -> TGF-β1/SMAD3 ↑ -> cell proliferation ↑ | [134] |
| miR-192, miR-200b/c | ↑ in glomeruli of STZ-treated and db/db mice | miR-192 in mouse mesangial cells ↑-> miR-200b/c ↑ -> TGF-β1 ↑ -> Col IA2 ↑, Col IVA1 ↑ | [135, 136] |
| miR-199b-3p | ↓ STZ mice | Downregulation of miR-199b-3p in HK-2 cells -> KDM6A ↑ -> E-cadherin ↓, TGF-β1 ↑, vimentin ↑, N-cadherin ↑ | [43] |
| miR-204 | ↓ in patients with DKD | miR-204 knockdown in mice -> TGF-β1 ↑, Col IA1 ↑, MCP-1 ↑ | [137] |
| miR-205 | ↓ in db/db mice | TGF-β1 downregulates miR-205 via HDAC2 -> fibronectin ↑, Col I ↑, SNAI1 ↑, CTGF ↑ | [66] |
| miR-342-3p | ↓ in db/db mice | miR-342-3p downregulation in mouse mesangial cells -> TGF-β1 ↑, fibronectin ↑, Col IV ↑, PTEN ↓ via SOX6 ↑ | [138] |
| miR-378 | ↓ in db/db mice | TGF-β1 reduces miR-378 in NRK-52E cells -> Col I, Col IV, α-SMA | [139] |
| miR-378 | ↓ in db/db mice | TGF-β1 decreases miR-378 in primary human mesangial cells -> mesangial cell expansion and proliferation | [139] |
| miR-1207-5p | miR-1207-5p upregulation in mesangial cells -> TGF-β1 ↑, PAI-1 ↑, fibronectin ↑ | [140] |
↑, upregulation; ↓, downregulation; Col, collagen; STZ, streptozotocin; TGF-R1, transforming growth factor-β receptor 1; CTGF, connective tissue growth factor; PAI, plasminogen activator inhibitor; WT-1, Wilms’ tumor 1; mTOR, mechanistic Target of Rapamycin; α-SMA, smooth muscle actin; DKD, diabetic kidney disease; HDAC, histone deacetylase; PTEN, Phosphatase and Tensin homolog; SIRT1, sirtuin 1; KDM6A, lysine demethylase 6A; MCP-1, monocyte chemoattractant protein-1; SOX, SRY-Box Transcription Factor.