Defect in amino acid transport reduces the production of erythropoietin and compromises the formation of red blood cells

Red blood cell production (erythropoiesis) depends on a key factor: erythropoietin, a hormone generated mainly in the kidney that regulates the formation of these blood cells.  Researchers led by Dr. Manuel Palacín and Dr. Susanna Bodoy at IRB Barcelona have now demonstrated that deficiency in SLC7A7 protein causes a reduction in erythropoietin and, consequently, a dysfunction in red blood cell production. The study was conducted in collaboration with expert groups on iron metabolism led by Dr. Günter Weiss (Medical University of Innsbruck) and Dr. Mayka Sánchez (Universitat Internacional de Catalunya).

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 Published in the journal Molecular Medicine, the work also concludes that these defects are not caused by the lack of SLC7A7 in hematopoietic cells themselves but by alterations linked to the kidney.

This finding allows a deeper understanding of the molecular bases of anaemia associated with Lysinuric Protein Intolerance (LPI). LPI is a rare disease caused by mutations in the Slc7a7 gene that lead to defective transport of neutral and basic amino acids.

Despite being a rare disease, LPI causes complications in multiple organs and systems. The main approach to treatment is through a low-protein diet combined with citrulline. However, patients often continue to present haematological and immunological alterations.

“Our results indicate that depletion of erythropoietin in the kidney is key to understanding the problems in red blood formation,” explains Dr. Palacín, head of the Amino Acid Transporters and Disease lab at IRB Barcelona and professor of the Biochemistry and Molecular Biology Department of the Faculty of Biology at the University of Barcelona.  “This paves the way for new therapeutic approaches specifically aimed at correcting the production of erythropoietin,” he adds.

To undertake the study, the team used mice with complete deletion of the Slc7a7 gene, as well as models in which the deletion was restricted exclusively to different types of blood cells. The analyses showed that the lack of SLC7A7 at the systemic level caused a disruption of erythropoiesis and an increase in iron levels. However, the limited deficiency in different types of blood cells did not cause these issues, thereby pointing to the kidney as the origin. Furthermore, bone marrow transplants did not reverse the haematological defects, thus supporting the notion that the problem is extrinsic to hematopoietic cells.

The findings highlight the need to explore new therapeutic approaches that, beyond diet and citrulline supplementation, focus on restoring erythropoietin production to prevent the haematological complications of LPI.

Related article:
Defective Slc7a7 transport reduces erythropoietin compromising erythropoiesis
Judith Giroud-Gerbetant, Fernando Sotillo, Gonzalo Hernández, Irene Ruano, David Sebastián, Joana Fort, Mayka Sánchez, Günter Weiss, Neus Prats, Antonio Zorzano, Manuel Palacín, Susanna Bodoy
Molecular Medicine (2025) DOI: 10.1186/s10020-025-01100-0