The activation of JAK/STAT3 signaling and the complement system modulate inflammation in the primary human dermal fibroblasts of PXE patients

  • Previous studies revealed a link between inflammation and overactivation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling in syndromes associated with aging. Pseudoxanthoma elasticum (PXE), a rare autosomal-recessive disorder, arises from mutations in \(\textit {ATP-binding cassette subfamily C member 6 (ABCC6)}\). On a molecular level, PXE shares similarities with Hutchinson–Gilford progeria syndrome, such as increased activity of senescence-associated- beta-galactosidase or high expression of inflammatory factors. Thus, this study's aim was the evaluation of activated STAT3 and the influence of JAK1/2-inhibitor baricitinib (BA) on inflammatory processes such as the complement system in PXE. Analysis of activation of STAT3 was performed by immunofluorescence and Western blot, while inflammatory processes and complement system factors were determined based on mRNA expression and protein level. Our results assume overactivation of JAK/STAT3 signaling, increased expression levels of several complement factors and high C3 protein concentration in the sera of PXE patients. Supplementation with BA reduces JAK/STAT3 activation and partly reduces inflammation as well as the gene expression of complement factors belonging to the C1 complex and C3 convertase in PXE fibroblasts. Our results indicate a link between JAK/STAT3 signaling and complement activation contributing to the proinflammatory phenotype in PXE fibroblasts.

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Author:Christopher LindenkampGND, Ricarda PlümersORCiDGND, Michel Robin OsterhageGND, Olivier VanakkerORCiDGND, Judith Van WynsbergheGND, Cornelius KnabbeGND, Doris HendigORCiDGND
Parent Title (English):Biomedicines
Place of publication:Basel
Document Type:Article
Date of Publication (online):2024/03/19
Date of first Publication:2023/09/29
Publishing Institution:Ruhr-Universität Bochum, Universitätsbibliothek
Tag:Open Access Fonds
JAK/STAT3; baricitinib; complement system; pseudoxanthoma elasticum
Issue:10, Article 2673
First Page:2673-1
Last Page:2673-17
Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum.
Institutes/Facilities:Herz- und Diabeteszentrum NRW
Herz- und Diabeteszentrum NRW, Institut für Laboratoriums- und Transfusionsmedizin
Dewey Decimal Classification:Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit
open_access (DINI-Set):open_access
Licence (English):License LogoCreative Commons - CC BY 4.0 - Attribution 4.0 International