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
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.