Table 2.

miRNAs involved in diabetes-related renal inflammation and fibrogenesis

Types	Functions involved	miRNAs	Expression levels	Target genes	Mechanisms	Ref
T1DN-related miRNAs	Renal Inflammation	miR-21	Upregulation	TIMP3	upregulation of miR-21 enhanced the excretion of pro-inflammatory factors by repressing the expression of TIMP3	[96]
		miR-146a	Upregulation	IRAK1/TRAF6	upregulation of miR-146a promoted NF-kB mediated upregulation of pro-inflammatory cytokines by negative feedback to Irak1 and Traf6	[97]
		miR-146a	Downregulation	Nox4	miR‑146a/Nox4 decreases ROS generation and inflammation and prevents DN	[98]
	Renal Fibrosis	miR-192	Upregulation	GLP1R	upregulation of miR-192 exerted its pro-fibrotic effects by directly targeting GLP1R	[99, 100]
		miR-214	Upregulation	PTEN	upregulation of miR-214 contributed to renal cell hypertrophy and matrix protein expression by directly acting on PTEN	[101]
		miR-22	Upregulation	PTEN	upregulation of miR-22 promoted renal tubulointerstitial fibrosis by suppressing autophagy partially via targeting PTEN	[102]
		miR-382	Upregulation	FOXO1	upregulation of miR-382-induced glomerular mesangial cell proliferation and ECM accumulation by targeting FOXO1	[103]
		miR-137	Downregulation	Notch1	miR-137 inhibition aggravated ECM protein accumulation via directly targeting Notch1	[104]
	Both inflammation and fibrosis	miR-455-3p	Downregulation	ROCK2	downregulated miR-455-3p aggravated the progression of renal inflammation and fibrosis through promoting ROCK2 expression	[105]
T2DN related miRNAs	Renal Inflammation	miR-146a	Upregulation	IRAK1/TRAF6	upregulation of miR-146a promoted NF-kB mediated upregulation of pro-inflammatory cytokines by negative feedback to Irak1 and Traf6	[97]
	Renal Fibrosis	miR-133b/199b	Upregulation	Sirt 1	upregulation of miR-133b and miR-199b enhanced TGF-β1-induced epithelial to mesenchymal transition and renal fibrosis by targeting SIRT1 in diabetic nephropathy	[107]
		miR-23a	Upregulation	SnoN	upregulation of miR-23a promoted high glucose-induced EMT and renal fibrogenesis by down-regulation of SnoN	[112]
		miR-30e	Downregulation	GLIPR-2	miR-30e inhibited GLIPR-2 and then promoted the proliferation of RTECs and inhibited EMT, ultimately leading to renal fibrosis in DN	[109]
		miR-93	Downregulation	Orai1	downregulation of microRNA-93-induced TGF-b1-induced EMT and renal fibrogenesis by down-regulation of Orai1	[110]
	Both inflammation and fibrosis	miR-29b	Downregulation	SP1/Smad-3/NF-κB	miR-29b played a protective role in diabetic kidney disease by the inhibition of Sp1 expression, TGF-β/Smad3-dependent renal fibrosis, and NF-κB-driven renal inflammation	[106]
	Renal Inflammation	miR-423-5p	Downregulation	Nox4	miR-423-5p suppressed high-glucose induced podocyte injury and inhibited ROS generation by targeting Nox4	[95]
Not mentioned	Renal Fibrosis	miR-4490	Upregulation	PSMA6	upregulation of miRNA-4490 regulated PSMA6 mRNA level post-transcriptionally	[94]
		miR-326-3p	Downregulation	FcγRIII	miR-326-3p ameliorates high glucose and ox-LDL-IC-induced fibrotic injury in renal mesangial cells by targeting FcγRIII	[113]
	Both inflammation and fibrosis	miR-199a-5p	Upregulation	Klotho	upregulated expression of miR-199a-5p decreased Klotho expression, resulting in activating the TLR4/NF-kB p65/NGAL signaling pathways and the downstream fibrosis and inflammation in HG-induced rat mesangial cells	[108]