We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Hepatocyte growth factor activator inhibitor type 2 (HAI-2) modulates hepcidin expression by inhibiting the cell surface protease matriptase-2.
- Authors
MAURER, Eva; GÜTSCHOW, Michael; STIRNBERG, Marit
- Abstract
Matriptase-2, a recently identified cell surface protease, is the key enzyme of iron homoeostasis modulating the expression of the liver peptide hormone hepcidin. HAI (hepatocyte growth factor activator inhibitor) types 1 and 2 (HAI-1 and HAI-2 respectively) have been shown to inhibit the close homologue, i.e. matriptase. By co-expressing matriptase-2 and the inhibitor HAI-2 we have identified HAI-2 displaying high inhibitory potential against matriptase-2 at the cell surface as well as in conditioned medium. Accordingly, complex formation between matriptase-2 and HAI-2 was demonstrated by isolation of the complex via immobilizing either HAI-2 or matriptase-2 from lysates and conditioned medium of co-expressing cells. Furthermore, HAI-2 indirectly influences the expression of the hepcidinencoding gene HAMP. The inhibitor abrogates the matriptase- 2-mediated suppression of HAMP expression, presumably by inhibiting the supposed potential of matriptase-2 to cleave membrane-bound HJV (haemojuvelin). Taken together, the results of the present study have characterized HAI-2 as an inhibitor of matriptase-2 that modulates the synthesis of hepcidin and provides new insights into the regulatory mechanism of iron homoeostasis, with clinical importance for a treatment of iron overload diseases.
- Subjects
MATRIPTASE; PROTEOLYTIC enzymes; HEPCIDIN; HEPATOCYTE growth factor; CELLULAR signal transduction; SERINE proteinases
- Publication
Biochemical Journal, 2013, Vol 450, Issue 3, p583
- ISSN
0264-6021
- Publication type
Article
- DOI
10.1042/BJ20121518