However, our studies have demonstrated that the promoter regions of the genes encoding EPO and HIF2α are highly methylated in MF-REP cells, and the expression of these genes is epigenetically silenced with CKD progression.
Compared to blood loss, anemia in young CKD rats is associated with inappropriate responses in the HIF-EPO-EPO-R axis: kidney HIF2α and renal EPO are not increased, BM and bone EPOR levels, as well as bone pSTAT5 response to EPO are reduced.
In conclusion, late-stage renal tubular HIF-2α activation has protective effects on renal fibrosis and the resultant renal dysfunction, thus it could represent a therapeutic target in late stage of CKD.