Figure 1. A summary of the possible roles that all-trans retinoic acid (ATRA) and Roflumilast (PDE4) may have to prevent the progression of HIVAN in HIV-Tg₂₆ mice.

Zhong et al.¹ showed that ATRA + PDE4 prevented the progression of HIVAN in Tg mice by blocking the de-differentiation and proliferation of podocytes through a cAMP/PKA/CREB dependent mechanisms that is independent of HIV-1 genes (highlighted in red color). Based on the pathogenesis of the renal disease in Tg₂₆ mice^3–5, and the known beneficial effects of these drugs in other experimental models of renal diseases ^6–8, we have highlight additional pathological pathways (black color) that might be affected as well. Abbreviations: ATRA = all-trans retinoic acid analogs; PDE4 = cyclic nucleotide phosphodiesterase-4 inhibitor; cAMP = cyclic adenosine monophosphate; FGF-2 = Fibroblast Growth Factor-2; HSGP = heparan sulfate proteoglycans; ECM = extracelllular matrix proteins; MCP-1 = Monocyte Chemoattractant Protein 1; AP-1= Activator Protein-1; NFkB = Nuclear Factor Kappa B; TGF-β = Transforming Growth Factor Beta; VEGF-A = Vascular Endothelial Cell Growth Factor-A; FSGS= Focal Segmental Glomerulosclerosis; Ras = rat sarcoma G protein; Raf = rapidly accelerated fibrosarcoma protein kinase; MEK = mitogen activated protein kinase / Erk kinase; MAPK-P = mitogen-activated protein kinase - phosphorylated / ERK-P; MKP-1 = mitogen activated protein kinase phosphatase-1; PKA = protein kinase A; RAR α = retinoic acid receptor alpha; RARE = retinoid acid responsive element; CREB = cAMP responsive element binding protein.