Tight junction disruption and the pathogenesis of the chronic complications of diabetes mellitus: A narrative review

Table 1 Drugs used to decrease proteinuria and progressive kidney disease and their effects on slit diaphragms /tight junction proteins

Drug	Type	Mechanism of action
Spironolactone[82]	Mineralocorticoid inhibitor	Decrease oxidative stress
		Prevent decrease of claudin-5 in glomeruli
		Prevent decrease of claudin-2 and occludin in PT
Simvastatin[85]	Inhibits HMG-CoA reductase	Inhibit RhoA/ROCK1 signaling
		Increase occludin expression
		Restore ZO-1 localization
atRA[94]	Retinoid	Decrease oxidative stress
		Prevent decrease of claudin-5 in glomeruli
		Prevent decrease of claudin-2 and occludin in PT
Lisinopril[97]	ACE inhibitor	Preserve glomerular ZO-1 distribution
Irbesartan[107]	Antagonist	Avoid nephrin depletion on SD
	Ang II receptor
Sitagliptin[108]	Inhibits DPP-4	Decrease levels of mitochondrial ROS, ameliorate reduction of claudin-5 in GEC
Sinomenine[109]	Alkaloid isolated from the root of Sinomenium acutum	Attenuate ROS level, tight junction dysfunction and RhoA/ROCK activation

ACE: Angiotensin converting enzyme; Ang: Angiotensin; atRA: All-trans retinoic acid; DPP-4: Dipeptidyl peptidase 4; GEC: Glomerular endothelial cells; HMG-CoA: 3-hydroxy-3-methylglutaryl coenzyme A; PT: Proximal tubule; ROS: Reactive oxygen species; SD: Slit diaphragms; ZO: Zonula occludens.