Table 1.

Therapeutic agents with direct effects on the podocyte

Therapeutic Agents	References	Models	Molecular Target in Podocytes
RAS inhibitors	(24, 44, 55, 56)	Rat model (Ren2, transgenic), murine and human podocytes	AKT phosphorylation leads to actin stabilization Reduce oxidative stress Inhibit MAPK/ERK signaling
Glucocorticoids	(16, 20, 38, 51, 52, 57, 58)	Murine and human podocytes, murine model (antiglomerular antibody)	Increase RhoA activity with stabilization of actin cytoskeleton Reduces podocyte apoptosis Restore Bcl-2 expression Reduce p21, p53, Il-6, Vegf expression Restores synthesis of glycosylated nephrin
Calcineurin inhibitors	(12, 45, 53)	Mouse model (LPS, transgenic mice), murine and human podocytes	Restore ZO-1 expression Prevents synaptopodin from cathepsin-L mediated degradation leading to preservation of phosphorylated synaptopodin and subsequent RhoA-mediated stabilization of actin stress fibers Reduces calcium influx in the podocyte by downregulating TRPC6 expression Inhibit NFAT signaling in the podocyte
Rituximab	(15)	Human podocytes, FSGS patient cohorts	Rescues SMPDL-3b expression and prevents actin cytoskeleton derangement and podocyte apoptosis
Abatacept	(41, 59)	Mouse model (LPS), human podocytes, FSGS patient cohorts	Inhibits B7-1 signaling and restores β1 integrin levels
ACTH	(5, 28, 39)	Rat model (PHN), pediatric cohorts with nephrotic syndrome	Binds to MC1R and attenuates oxidative stress
Retinoic acid	(21, 27, 30, 32, 37, 40, 50, 61–63)	Human podocytes, murine models (HIVAN, ADR, LPS)	Binds to RARα and activates cAMP pathway Induce KLF15 expression Restores podocyte differentiation markers Induce transition of parietal epithelial cells to podocytes Attenuates podocyte apoptosis

FSGS, focal segmental glomerular sclerosis; PHN, passive Heymann nephritis; HIVAN, HIV-associated nephropathy; ADR, adriamycin; ZO-1, zonula occludens-1; TRPC6, transient receptor potential cation channel, subfamily C, member 6; NFAT, nuclear factor of activated T-cell; SMPDL, sphingomyelinase-like phosphodiesterase receptor; MC1R, melancortin 1 receptor; RARα, retinoic acid receptor alpha; KLF15, Krüppel-like factor 15.