Akhtar-Schaefer, Isha, Reuten, Raphael, Koch, Manuel, Pietsch, Markus and Langmann, Thomas (2019). AMD-Associated HTRA1 Variants Do Not Influence TGF-beta Signaling in Microglia. S. 3 - 8. CHAM: SPRINGER INTERNATIONAL PUBLISHING AG. ISSN 2214-8019

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Abstract

Genetic variants of high-temperature requirement A serine peptidase 1 (HTRA1) and age-related maculopathy susceptibility 2 (ARMS2) are associated with age-related macular degeneration (AMD). One HTRA1 single nucleotide polymorphism (SNP) is situated in the promotor region (rs11200638) resulting in increased expression, while two synonymous SNPs are located in exon 1 (rs1049331:C > T, rs2293870:G > T). HtrA1 is known to inhibit transforming growth factor-beta (TGF-beta) signaling, a pathway regulating quiescence of microglia, the resident immune cells of the brain and retina. Microglia-mediated immune responses contribute to AMD pathogenesis. It is currently unclear whether AMD-associated HTRA1 variants influence TGF-beta signaling and microglia phenotypes. Here, we show that an HtrA1 isoform carrying AMD-associated SNPs in exon 1 exhibits increased proteolytic activity. However, when incubating TGF-beta-treated reactive microglia with HtrA1 protein variants, neither the wildtype nor the SNP-associated isoforms changed microglia activation in vitro.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Akhtar-Schaefer, IshaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reuten, RaphaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koch, ManuelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pietsch, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Langmann, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-159858
DOI: 10.1007/978-3-030-27378-1_1
Title of Book: Advances in Experimental Medicine and Biology
Series Name: Adv.Exp.Med.Biol.
Volume: 1185
Page Range: S. 3 - 8
Date: 2019
Publisher: SPRINGER INTERNATIONAL PUBLISHING AG
Place of Publication: CHAM
ISSN: 2214-8019
ISBN: 978-3-030-27378-1; 978-3-030-27377-4
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MACULAR DEGENERATION; SUSCEPTIBILITY; IMPAIRMultiple languages
Medicine, Research & Experimental; OphthalmologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/15985

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