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
Full text not available from this repository.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 | ||||||||||||||||||||||||
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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 | ||||||||||||||||||||||||
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Refereed: | Yes | ||||||||||||||||||||||||
URI: | http://kups.ub.uni-koeln.de/id/eprint/15985 |
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