| 1. |
- Fex Svenningsen, Åsa, et al.
(författare)
-
Macrophage migration inhibitory factor (MIF) modulates trophic signaling through interaction with serine protease HTRA1
- 2017
-
Ingår i: Cellular and Molecular Life Sciences (CMLS). - : Springer Science and Business Media LLC. - 1420-682X .- 1420-9071. ; 24, s. 4561-4572
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 2. |
- Hjæresen, Simone, et al.
(författare)
-
High temperature requirement A1 and macrophage migration inhibitory factor in the cerebrospinal fluid; a potential marker of conversion from relapsing-remitting to secondary progressive multiple sclerosis
- 2024
-
Ingår i: Journal of the Neurological Sciences. - 0022-510X .- 1878-5883. ; 457
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Predictive and prognostic biomarkers for multiple sclerosis (MS) remain a significant gap in MS diagnosis and treatment monitoring. Currently, there are no timely markers to diagnose the transition to secondary progressive MS (SPMS). Objective: This study aims to evaluate the discriminatory potential of the High temperature requirement serine protease (HTRA1)/Macrophage migration inhibitory factor (MIF) cerebrospinal fluid (CSF) ratio in distinguishing relapsing-remitting (RRMS) patients from SPMS patients. Methods: The MIF and HTRA1 CSF levels were determined using ELISA in healthy controls (n = 23), RRMS patients before (n = 22) and after 1 year of dimethyl fumarate treatment (n = 11), as well as in SPMS patients before (n = 11) and after 2 years of mitoxantrone treatment (n = 7). The ability of the HTRA1/MIF ratio to discriminate the different groups was determined using receiver operating curve (ROC) analyses. Results: The ratio was significantly increased in treatment naïve RRMS patients while decreased again in SPMS patients at baseline. Systemic administrated disease modifying treatment (DMT) only significantly affected the ratio in RRMS patients. ROC analysis demonstrated that the ratio could discriminate treatment naïve RRMS patients from SPMS patients with 91% sensitivity and 100% specificity. Conclusion: The HTRA1/MIF ratio is a strong candidate as a MS biomarker for SPMS conversion.
|
|
| 3. |
- Ulrichsen, Maj, et al.
(författare)
-
Sortilin Modulates Schwann Cell Signaling and Remak Bundle Regeneration Following Nerve Injury
- 2022
-
Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 16
-
Tidskriftsartikel (refereegranskat)abstract
- Peripheral nerve regeneration relies on the ability of Schwann cells to support the regrowth of damaged axons. Schwann cells re-differentiate when reestablishing contact with the sprouting axons, with large fibers becoming remyelinated and small nociceptive fibers ensheathed and collected into Remak bundles. We have previously described how the receptor sortilin facilitates neurotrophin signaling in peripheral neurons via regulated trafficking of Trk receptors. This study aims to characterize the effects of sortilin deletion on nerve regeneration following sciatic crush injury. We found that Sort1(-)(/)(-) mice displayed functional motor recovery like that of WT mice, with no detectable differences in relation to nerve conduction velocities and morphological aspects of myelinated fibers. In contrast, we found abnormal ensheathment of regenerated C-fibers in injured Sort1(-)(/)(-) mice, demonstrating a role of sortilin for Remak bundle formation following injury. Further studies on Schwann cell signaling pathways showed a significant reduction of MAPK/ERK, RSK, and CREB phosphorylation in Sort1(-)(/)(-) Schwann cells after stimulation with neurotrophin-3 (NT-3), while Schwann cell migration and myelination remained unaffected. In conclusion, our results demonstrate that loss of sortilin blunts NT-3 signaling in Schwann cells which might contribute to the impaired Remak bundle regeneration after sciatic nerve injury.
|
|
