Table 1.

Summary of the renoprotective effects of PACAP against different stressors. (↑ increasing effect, ↓ decreasing effect).

Harmful Stimulus/Disease	Observed Effect	Reference(s)
In Vitro
oxidative stress	↓ oxidative stress-induced cell death in rat renal cells	[39]
cyclosporine A	↓ morphological changes ↓ cyclosporine a-induced TGF-β1 ↓ apoptosis	[40]
gentamicin	↓ gentamicin-induced cell death in HK-2 cells	[41]
cisplatin	↓ cisplatin-induced apoptosis in mouse renal proximal tubule cells	[42]
LPS exposure	↓ proinflammatory cytokines in podocytes	[43]
hypoxia	↓ cytokine activation ↓ cell death	[44]
kappa light chains	↓ IL-6, TNF-α ↓ p38 phosphorylation	[45]
In Vivo
Ischemia/reperfusion	↑ renal function and kidney morphology in warm ischemia	[46]
	↓ tubular degeneration and mortality	[47]
	↓ I/R-induced increase of CNTF, fractalkine, sICAM-1, RANTES, TIMP-1 and MIP-3α ↓ Bcl-2	[48]
	↓ SOD and glutathione	[39]
	↓renal failure, histological damage, neutrophil influx and tubule cell apoptosis	[44]
	gender-different protective effect ↓ tubular damage ↓ fractalkine, L-selectin, RANTES, sICAM-1, thymus chemokine, CNTF ↑ SOD in females influences BMP signaling	[49]
	in PACAP deficiency after I/R: ↓ SOD level more severe histological damage elevated expression of: BLC, G-CSF, IL-1ra, IL-6, KC, MCP-1, MIP-2, TIMP-1, TREM-1 decreased expression of: sICAM-1, interferon-γ, IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-7, IL-10, IL-13, IL-16, IL-17, IL-23, IL-27, IP-10, M-CSF, MCP-5, MIG, SDF-1	[50,51]
cyclosporine A	↓ apoptosis ↓ renal injury and fibrosis ↓ extracellular matrix mRNA expression reverse activation of epithelial mesenchymal transition markers ↓ ROS	[40]
diabetic nephropathy	↓ histological damage ↓ cytokine activation	[52,53]
	↓ TNF-α	[53]
	↑ pAkt, pERK1/2 ↓ collagen IV, TGF-β-1 ↓ pp38MAPK, cleaved caspase-3 ↓ p60 subunit of NFκB ↑ GSH no focal segmental glomerular basement membrane thickening ↓ podocyte injury	[54]
gentamicin	↓ TNF-α production	[53]
cisplatin	↓tubular damage ↑renal function ↑ tubular cell regeneration	[42]
amyloidosis	pre-senile amyloidosis in PACAP deficiency	[55,56]