Matriptase-2 and Hemojuvelin in Hepcidin Regulation: In Vivo Immunoblot Studies in Mask Mice

0542251 - BTÚ 2022 RIV CH eng J - Journal Article
Krijt, J. - Frýdlová, J. - Gurieva, I. - Přikryl, P. - Báječný, M. - Steinbicker, A. U. - Vokurka, M. - Truksa, Jaroslav
Matriptase-2 and Hemojuvelin in Hepcidin Regulation: In Vivo Immunoblot Studies in Mask Mice.
International Journal of Molecular Sciences. Roč. 22, č. 5 (2021), č. článku 2650. E-ISSN 1422-0067
R&D Projects: GA ČR(CZ) GA18-13103S; GA MŠMT(CZ) LQ1604; GA MŠMT(CZ) ED1.1.00/02.0109
Institutional support: RVO:86652036
Keywords : hepcidin * transferrin receptor * neogenin * Hjv
OECD category: Biochemistry and molecular biology
Impact factor: 6.208, year: 2021
Method of publishing: Open access
https://www.mdpi.com/1422-0067/22/5/2650

Matriptase-2, a serine protease expressed in hepatocytes, is a negative regulator of hepcidin expression. The purpose of the study was to investigate the interaction of matriptase-2 with hemojuvelin protein in vivo. Mice lacking the matriptase-2 proteolytic activity (mask mice) display decreased content of hemojuvelin protein. Vice versa, the absence of hemojuvelin results in decreased liver content of matriptase-2, indicating that the two proteins interact. To further characterize the role of matriptase-2, we investigated iron metabolism in mask mice fed experimental diets. Administration of iron-enriched diet increased liver iron stores as well as hepcidin expression. Treatment of iron-overloaded mask mice with erythropoietin increased hemoglobin and hematocrit, indicating that the response to erythropoietin is intact in mask mice. Feeding of an iron-deficient diet to mask mice significantly increased spleen weight as well as the splenic content of erythroferrone and transferrin receptor proteins, indicating stress erythropoiesis. Liver hepcidin expression was decreased, expression of Id1 was not changed. Overall, the results suggest a complex interaction between matriptase-2 and hemojuvelin, and demonstrate that hepcidin can to some extent be regulated even in the absence of matriptase-2 proteolytic activity.
Permanent Link: http://hdl.handle.net/11104/0319715