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Article: Macrophage migration inhibitory factor (MIF) modulates trophic signaling through interaction with serine protease HTRA1

Fex Svenningsen, Åsa / Anna Lahn Sørensen / Eirikur Benedikz / Ha Uyen Buu Huynh / Jesper Bonnet Moeller / Malin Andersson / Maria Louise Elkjær / Nellie Martin / Simone Hjæresen / Solveig Beck Nielsen / Svenja Löring / Uffe Holmskov / Zsolt Illes

Cellular and molecular life sciences. 2017 Dec., v. 74, no. 24

2017  

Abstract: Macrophage migration inhibitory factor (MIF), a small conserved protein, is abundant in the immune- and central nervous system (CNS). MIF has several receptors and binding partners that can modulate its action on a cellular level. It is upregulated in ... ...

Abstract Macrophage migration inhibitory factor (MIF), a small conserved protein, is abundant in the immune- and central nervous system (CNS). MIF has several receptors and binding partners that can modulate its action on a cellular level. It is upregulated in neurodegenerative diseases and cancer although its function is far from clear. Here, we report the finding of a new binding partner to MIF, the serine protease HTRA1. This enzyme cleaves several growth factors, extracellular matrix molecules and is implicated in some of the same diseases as MIF. We show that the function of the binding between MIF and HTRA1 is to inhibit the proteolytic activity of HTRA1, modulating the availability of molecules that can change cell growth and differentiation. MIF is therefore the first endogenous inhibitor ever found for HTRA1. It was found that both molecules were present in astrocytes and that the functional binding has the ability to modulate astrocytic activities important in development and disease of the CNS.
Keywords astrocytes ; cell growth ; central nervous system ; extracellular matrix ; growth factors ; macrophage migration inhibitory factors ; neoplasms ; neurodegenerative diseases ; proteolysis ; receptors ; serine proteinases
Language English
Dates of publication 2017-12
Size p. 4561-4572.
Publishing place Springer International Publishing
Document type Article
ZDB-ID 1358415-7
ISSN 1420-9071 ; 1420-682X
ISSN (online) 1420-9071
ISSN 1420-682X
DOI 10.1007/s00018-017-2592-z
Shelf mark
Z 4' 47/14: Show issues
Database NAL-Catalogue (AGRICOLA)

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