Exploring a novel mechanism for targeting β-arrestin-2 in the management of diabetic nephropathy

Table 1 Current landscape of treatment options for diabetic nephropathy

Category of DN therapies	Therapeutic targets	Mechanism of action	Ref.
Established therapies	RAS blockers (ACEi/ARBs)	Suppress renal inflammation, reduce angiotensin II-mediated vasoconstriction, and alleviate glomerular hypertension	[35,36]
	SGLT2 inhibitors	Increase urinary sugar excretion, reduce hyperglycemia and glomerular hyperfiltration by inhibiting sodium-glucose co-transport	[37]
	GLP-1 agonists	Lower hyperglycemia by promoting insulin secretion and inhibiting glucagon secretion	[38,39]
	MRAs	Inhibit oxidative stress, inflammation and fibrosis via blocking MR overactivation	[40]
	Endothelin antagonists	Improve renal microcirculation and reduce proteinuria by alleviating inflammation, fibrosis and podocyte injury	[41,42]
	DPP-4 inhibitors	Improve glycaemic control, reduce kidney damage, proteinuria and vascular inflammation through blocking GLP-1 degradation	[43]
Emerging therapies	Phosphodiesterase inhibitors	Reduce proteinuria, inflammation and fibrosis	[44]
	VDR agonists	Ameliorate the damage to proximal tubular epithelial cells, reduce fibrosis and proteinuria	[45,46]
	Selective PPAR agonists (PPAR-γ/PPAR-α/δ)	Regulate metabolism, reduce hyperglycemia, proteinuria, inflammation and fibrosis	[47,48]
	TGF-β inhibitors	Prevent fibrosis and extracellular matrix accumulation	[49,50]
	β-arrestin-2 inhibitors	Inhibit ER stress-induced renal injury, alleviate inflammation and fibrosis	[28,34]

MRAs: Mineralocorticoid receptors antagonists; DN: Diabetic nephropathy; ER: Endoplasmic reticulum.