Macrophage migration inhibitory factor (MIF) modulates trophic signaling through interaction with serine protease HTRA1.
Macrophage migration inhibitory factor (MIF) modulates trophic signaling through interaction with serine protease HTRA1.
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DOI：
10.1007/s00018-017-2592-z
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发表时间：
2017-12
期刊：
影响因子：
--
通讯作者：
Benedikz E
中科院分区：
文献类型：
--
作者：
Fex Svenningsen Å;Löring S;Sørensen AL;Huynh HUB;Hjæresen S;Martin N;Moeller JB;Elkjær ML;Holmskov U;Illes Z;Andersson M;Nielsen SB;Benedikz E
巨噬细胞移动抑制因子(MIF)是一种小而保守的蛋白质，在免疫和中枢神经系统(CNS)中含量丰富。MIF有几个受体和结合伙伴，可以在细胞水平上调节其作用。它在神经退行性疾病和癌症中表达上调，尽管它的功能还远不清楚。在这里，我们报告了MIF的一个新的结合伙伴，丝氨酸蛋白酶HTRA1。这种酶分解几种生长因子和细胞外基质分子，并与一些与MIF相同的疾病有关。我们发现，MIF和HTRA1结合的功能是抑制HTRA1的蛋白分解活性，调节可以改变细胞生长和分化的分子的可用性。因此，MIF是迄今发现的第一个针对HTRA1的内源性抑制物。研究发现，这两个分子都存在于星形胶质细胞中，并且这种功能结合具有调节星形胶质细胞活动的能力，这些活动在中枢神经系统的发育和疾病中起重要作用。本文的在线版本(doi：10.1007/s000180172592z)包含补充材料，授权用户可以使用。
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. The online version of this article (doi:10.1007/s00018-017-2592-z) contains supplementary material, which is available to authorized users.
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