Granzyme B cleaves tenascin-C to release its C-terminal domain in rheumatoid arthritis.

ABSTRACT: Rheumatoid arthritis (RA) is a common autoimmune disorder characterized by exacerbated joint inflammation. Despite the well-documented accumulation of the serine protease granzyme B (GzmB) in RA patient biospecimens, little is understood pertaining to its role in pathobiology. In the present study, tenascin-C (TNC) - a large, pro-inflammatory extracellular matrix glycoprotein - was identified as a substrate for GzmB in RA. GzmB cleaves TNC to generate 3 fragments in vitro: a 130 kDa fragment that remains anchored to the matrix and 2 solubilized fragments of 70 and 30 kDa. Mass spectrometry results suggested that the 30 kDa fragment contained the pro-inflammatory TNC C-terminal fibrinogen-like domain. In the synovial fluids of patients with RA, soluble levels of GzmB and TNC were significan

SUBMITTER: Aubert A 

PROVIDER: S-EPMC11623945 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature