VEGF expands erythropoiesis via hypoxia-independent induction of erythropoietin in noncanonical perivascular stromal cells.

ABSTRACT: Insufficient erythropoiesis due to increased demand is usually met by hypoxia-driven up-regulation of erythropoietin (Epo). Here, we uncovered vascular endothelial growth factor (VEGF) as a novel inducer of Epo capable of increasing circulating Epo under normoxic, nonanemic conditions in a previously unrecognized reservoir of Epo-producing cells (EPCs), leading to expansion of the erythroid progenitor pool and robust splenic erythropoiesis. Epo induction by VEGF occurs in kidney, liver, and spleen in a population of Gli1⁺SMA⁺PDGFRβ⁺ cells, a signature shared with vascular smooth muscle cells (VSMCs) derived from mesenchymal stem cell-like progenitors. Surprisingly, inhibition of PDGFRβ signaling, but not VEGF signaling, abrogated VEGF-induced

SUBMITTER: Greenwald AC 

PROVIDER: S-EPMC6314526 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature