Macrophage Migration Inhibitory Factor (MIF) Modulates Trophic Signaling Through Interaction with Serine Protease HTRA1

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2017 Jul 21

PMID 28726057

Citations 9

Authors

Asa Fex Svenningsen

Svenja Loring

Anna Lahn Sorensen

Ha Uyen Buu Huynh

Simone Hjaeresen

Nellie Martin

Jesper Bonnet Moeller

Maria Louise Elkjaer

Uffe Holmskov

Zsolt Illes

Malin Andersson

Solveig Beck Nielsen

Eirikur Benedikz

Affiliations

Soon will be listed here.

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.

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