The JAK/STAT pathway is activated in systemic sclerosis and is effectively targeted by tofacitinib.

ABSTRACT:

Rationale

Fibrosis leads to failure of the skin, lungs, and other organs in systemic sclerosis; accounts for substantial morbidity and mortality; and lacks effective therapy. Myofibroblast activation underlies organ fibrosis, but the key extracellular cues driving persistence of the process remain incompletely characterized.

Objectives

The objectives were to evaluate activation of the IL6/JAK/STAT axis associated with fibrosis in skin and lung biopsies from systemic sclerosis patients and effects of the Food and Drug Administration-approved JAK/STAT inhibitor, tofacitinib, on skin and lung fibrosis in animal models.

Methods

Bioinformatic analysis showed that IL6/JAK/STAT3 and tofacitinib gene signatures were aberrant in biopsies from systemic sclerosis patients in fou

SUBMITTER: Wang W 

PROVIDER: S-EPMC8922593 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature