Table 2.

Potential strategies targeting EV-associated intercellular communication.

Intervention strategy	Representative target or agent	Primary intervention point	Principal experimental result	Evidence stage	Ref.
Cargo-sorting intervention	Epsin1/Dll4	Reduces Dll4 sorting into TEC-derived EVs	Attenuates macrophage Notch1 activation and pro-inflammatory responses	Comparatively strong mechanistic validation; acts mainly on the TEC-to-macrophage axis	(51)
Cargo-function intervention	miR-19b-3p, miR-199a-5p, miR-7002-5p, miR-21-5p, and TGF-β1 mRNA	Inhibits a defined EV cargo or its expression in donor cells	Reduces macrophage activation, impaired TEC autophagy, podocyte pyroptosis, and mesangial fibrosis	Preclinical mechanistic evidence; intervention level and cargo specificity differ among studies	(48, 49, 54, 58, 65)
Regulation of EV release	Rab27a, Rac1-Rab8a, and SESN2	Reduces TEC-derived EV output or directs multivesicular bodies toward the autophagy-lysosome pathway	Lowers inflammatory indices and attenuates kidney injury	Supportive preclinical evidence; targets also regulate membrane trafficking, autophagy, or stress responses independently of EVs	(73–75)
Modulation of macrophage state	GABA and Yi-Shen-Hua-Shi granules	Changes experimental macrophage state and EV cargo composition	Reduces injury-promoting miRNA; in the GABA model, also increases the miR-25-3p-related protective signal and attenuates podocyte injury	Preclinical intervention evidence; may also alter soluble secretion and cellular metabolism, and cross-axis effects remain untested	(60, 76)
Endogenous protective EV mechanism	EVs from reparative macrophages: lncRNA AFAP1-AS1 and miR-25-3p	Suppresses podocyte pyroptosis or improves autophagy	Improves high-glucose-associated podocyte injury phenotypes	State-related mechanistic model; supports a protective return signal but does not establish dynamic balance across the network	(61, 62)
Exogenous engineered EV formulation	RGD-Treg-Exos/miR-218-5p	Targets podocytes and promotes mitophagy	Attenuates podocyte injury and kidney damage in diabetic mice	Preclinical therapeutic-delivery evidence; does not establish an endogenous Treg-to-podocyte communication edge	(77)
Exogenous mesenchymal stromal cell (MSC)-EV formulation	MSC-derived EVs and multi-cargo signals including miR-99b-5p	Regulates autophagy, fibrosis-associated cell states, YAP, and ferroptosis	Attenuates inflammation, fibrosis, and kidney injury	Preclinical studies of diabetes-related kidney injury; multi-cargo and systemic effects limit direct intrarenal attribution, and no human intervention evidence exists	(78–82)