Table 3.

The mechanisms of macrophage-derived exosomes

Action pathway	Source of exosomes	Exosome content	Experimental model	Route of administration	Biological function	Molecular mechanism	Application	References
Inflammation	Macrophages	Exos	Hyperglycemic skin injury SD rat	Subcutaneous injection	Inhibits inflammatory signaling in vivo	TNF-α, IL-6↓	Diabetic wound healing	[88]
	M2 macrophages	M2-Exos	Osteotomized db/db mice (T2DM)	Introduce the fracture site	Macrophages polarized from M1 to M2	PI3K/AKT↑	Diabetic bone wound healing	[89]
	IL-4 polarized human macrophages	MiR-146b-5p, miR-33-5p, miR-21-5p	Apoeh/h Ldlr-/- mice	Intraperitoneal injection	Drive mitochondrial cell signal transduction	TLR/NF-κB↓	Diabetic atherosclerosis	[90]
	High glucose-treated macrophages	HG-treated Raw264.7	High glucose-induced male C57BL/6 mice	Tail vein injection	Glomerulosclerosis and tubulointerstitial fibrosis	TGF-β, TNF-α, IL-1β↑	Aggravate diabetic nephropathy	[91]
	High glucose-treated macrophages	Raw264.7	Male-specific pathogen-free C57BL/6 mice	Tail vein injection	Promote mesangial expansion and renal fibrosis	TGF-β/SMAD3↑	Aggravate diabetic nephropathy	[92]
Insulin resistance	Adipose tissue macrophages	MiR-29a	High fat-induced male C57BL/6 mice	Intravenous injection	Damage insulin sensitivity	PPAR-d↑	Deterioration of condition	[93]
	Bone marrow macrophages	MiR-143-5p	High fat-induced mice	Lipopolysaccharide-induced RAW264.7 exosomes	Regulation of the insulin signaling pathway in hepatocytes results in insulin resistance	MKP5↓	Deterioration of condition	[94]
	M2 bone marrow-derived macrophages	MiR-690	High fat-induced male C57BL/6 mice	Tail vein injection	Promote cell insulin sensitivity	NADK↑	Improve insulin resistance	[95]
	Macrophages containing MALAT1	MALAT1	Male Wistar rat with an intraperitoneal injection of streptozotocin	Intracarotid injection	Reduce balloon injury	MiR-150-5p↓	Diabetic angiopathies	[97]
	Lipotoxicity-polarised macrophages	MiR-27-3p	High fat-induced male C57BL/6 mice	Intravenous injection	Reduce glucose tolerance and insulin sensitivity	MIRO1↓	Deterioration of condition	[98]