Does HIF increase EPO?

HIF-regulated genes are indicated in red. HIF-2 activation (either by hypoxia, pharmacologic means or as a result of mutations) induces renal and hepatic EPO synthesis, which leads to an increase in serum EPO levels and stimulation of erythropoiesis.

What does HIF-1 beta do?

HIF-1 recognizes and binds to hypoxia response elements (HRE) in the promoters of target genes including those involved in angiogenesis and cell proliferation such as vascular endothelial growth factor (VEGF) and erythropoietin.

What is the difference between HIF-1 and HIF-2?

In VHL-deficient renal cell carcinoma, overexpression and knockdown studies have shown that HIF-2α promotes tumor growth whereas HIF-1α inhibits tumor growth,103 and in some cancers, HIF-1 binds to and stabilizes p53 to mediate hypoxia-induced apoptosis, whereas HIF-2 suppresses p53 and promotes chemoresistance.

How is HIF-1 activated?

At the heart of the HIF-1 system, molecular oxygen reacts with HIF-α proteins in a way that switches their ability to interact with other proteins (Figure 1). The HIF-α chain is regulated by two enzymatic reactions in which molecular oxygen reacts with specific amino acid residues (7–9⇓⇓).

How do HIF inhibitors work?

Hypoxia-inducible factor (HIF) prolyl hydroxylase (PH) enzyme inhibitors are a new class of agents for the treatment of anemia in CKD. These agents work by stabilizing the HIF complex and stimulating endogenous erythropoietin production even in patients with end-stage kidney disease.

How do HIF stabilizers work?

In summary, HIF stabilizers increase Hb levels and TIBC, and decrease the levels of ferritin and hepcidin in NDD-CKD patients, indicating that these are safe for short-term use in the treatment of anemia in NDD-CKD patients.

How do HIF PH inhibitors work?

Does HIF activate VEGF?

HIF-1α is a transcription factor that under hypoxic conditions, accumulates in endothelial cells and can bind to VEGF gene promoter and induce VEGF gene expression. In order to activate the VEGF gene, HIF-1α must be transported to the nucleus.