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Hepatocyte growth factor activator inhibitor type 2 (HAI-2) modulates hepcidin expression by inhibiting cell surface protease matriptase-2.
MedLine Citation:
PMID:  23293962     Owner:  NLM     Status:  Publisher    
Matriptase-2, a recently identified cell surface protease is the key enzyme of iron homeostasis modulating the expression of the liver peptide hormone hepcidin. Hepatocyte growth factor activator inhibitors type 1 and 2 (HAI-1 and HAI-2) 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 media. 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 media of co-expressing cells. Furthermore, HAI-2 indirectly influences the expression of the hepcidin-encoding 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 hemojuvelin (HJV). Altogether, our study 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 homeostasis, with clinical importance for a treatment of iron overload diseases.
Eva Maurer; Michael Gütschow; Marit Stirnberg
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-8
Journal Detail:
Title:  The Biochemical journal     Volume:  -     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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