Event | Modulated associated event | Modulation in AKI | Molecular cause |
---|---|---|---|
RAAS activation | Angiotensin signalling | up | Cathepsin/kallikrein/kininogen activity, blood pressure, pH |
Vasoconstriction | Vasoconstrictors (endothelin, angiotensin, MMP2) | up | RAAS pathway induction, endothelial obstruction |
Ā | Vasodilators (NO) | down | NOS inhibition, reduced NO bioavailability by ROS activity |
Hyperglycaemia | Ā | up | 20-hydroxyeicosatetraenoic acid (20-HETE), Glycogen phosphorylase, PPARĪ³ |
Elevated blood pressure | Hypertension | up | Renin, 20-hydroxyeicosatetraenoic acid (20-HETE), mineralocorticoid receptor |
Hypoxia | HIF1Ī± | up | Induction by vasoconstriction and ECM accumulation |
Ā | NADPH oxidases | up | Induction by RAAS and PLCĪ² |
Ā | ROS levels | up | NAD(P)H oxidases, P450 isoforms, Xanthine dehydrogenase |
Ā | NFĪŗB activity | up | ROS-modulated activation |
Ā | Inflammation factors (TNFĪ±, TF, PAT1, MCP1) | up | NFĪŗB-mediated gene expression |
Ā | Inflammation and inflammatory response | up | JAK/STAT- and NFĪŗB-dependent gene activation, other pathways |
Ā | Atherogenesis, fibrinogenesis | up | TGFĪ² signalling and gene activation pathway |
Ā | ATP levels | down | Depletion by PMCA activity and others, and inhibition of de-novo ATP production |
Ā | NAD levels | down | Rundown by PARP |
Ā | Hypoxanthine levels | up | Metabolic shift from accumulated XMP, IMP and Inosine |
Ā | Necrosis | up | ROS, SOD, OH., DNA damage, PARP, NAD rundown |
PI3K modulation | PI3Kinase activity | down | Inhibition by Jnk and PKCĪ± |
Ā | Insulin signalling | down | Inhibition by RAAS and PPARĪ³ systems |
Accumulation of free and esterified cholesterol | Systemic stress response | up | LIPE inhibition by PP1 |
Na+/Cl- retention, increased luminal Na+ | Aldosterone/cortisol signalling events | up | Mineralocorticoid/Glucocorticoid-receptors, acting on Na+/Cl- pumps |
Ras activation | Ras signalling | up | Mineralocorticoid/Glucocorticoid-receptor-dependent gene activation, Angiotensin receptor signalling |
Cytoskeletal reorganization | ECM remodelling | up | Hsp27, ATP depletion, Rac1 activation, Ras mediated events |
Tubular cell dynamics | Infiltration of immature cells | up | Pro-apoptotic signals |