Table 3.
Role of IS in the regulation of renal anemia.
| The Pathophysiologic Roles of IS | Molecular Mechanisms | References |
|---|---|---|
| Impairment of erythropoiesis in a HIF dependent manner | Suppression of the EPO gene transcription during hypoxia | [43] |
| Stimulates eryptosis | Extracellular Ca2+ entry with subsequent stimulation of cell shrinkage and cell membrane scrambling | [66] |
| Might contribute to EPO resistance and endothelial dysfunction | IS inhibits EPO-Induced Phosphorylation of EPOR IS inhibits TSP-1 expression through suppression of the AKT phosphorylation |
[67] |
| Suppression of HIF activation | IS-induced AhR activation | [70] |
| Increased PCA in RBCs | Due to PS exposure and RBCs-derived microparticles release | [71] |
| EPO decrease | IS negatively regulates the EPO expression | [73] |
| IS-induced RBCs death | Through OAT2, and NADPH oxidase activity-dependent, and a GSH-independent mechanism | [75] |
Abbreviations: HIF, hypoxia-inducted factor; EPO, erythropoietin; EPOR, erythropoietin receptor; IS, indoxyl sulfate; TSP-1, Thrombospondin-1; AhR, the aryl hydrocarbon receptor; PCA, Procoagulant Activity; PS, Phosphatidylserine; RBCs, red blood cells; OAT2, Organic Anion Transporter 2; GSH, glutathione.